Restoration Of Function Research Articles

Phytostabilisation of arsenic contaminated gold mine waste using the native species Juncus usitatus, Poa labillardieri and Themeda triandra

Arsenic (As) contaminated gold mine waste represents a significant issue for ecosystem and human health, as it is a known carcinogen and environmental toxin. Bendigo in Victoria, Australia, has reported As concentrations up to 22,000 mg/kg, exceeding the national soil guidance values (100 mg/kg) by 220-fold. To reduce exposure and potential human health risk, remediation or risk management strategies are required. Traditional remediation, such as excavation and landfill, often fail to improve soil conditions and are expensive. Biological remediation using plants (phytoremediation) represents a cost-effective strategy that results in the restoration of soil function and ecosystem services. There is a need to identify native plants for phytoremediation as current research focuses on fern species, which are not suitable for Bendigo. This study aimed to identify a native phytostabilising plant by conducting a mesocosm experiment involving Juncus usitatus, Poa labillardieri, and Themeda triandra. Plants grew in mine waste for 100 days; all survived and bioaccumulated As in the roots (phytostabilisation). Poa labillardieri grew significantly more biomass (roots 0.24 ± 0.01 g; shoots 0.22 ± 0.03 g (d/w)) and bioaccumulated the most As (~ 100 mg/kg plant biomass). The bacterial community was investigated to assess soil health and As association. The rhizosphere microbiota stabilised after root colonisation for Poa labillardieri and Themeda triandra, as indicated by richness and evenness changes. The two dominant phyla were Actinobacteriota and Proteobacteria, which displayed As tolerance. A keystone taxon, Latescibacterota, exhibited a positive relative association with As remediation. Poa labillardieri is a good candidate for future phytostabilisation trials.

Research on the Robustness of Command and Control Networks under Cascading Failures

The current analysis of cascading failures in command and control networks pays little attention to their roles and mechanisms, resulting in challenges in quantifying survivability evaluation metrics and limiting practical application. To address these issues, this paper designs a command and control network model with a recovery strategy to improve the scientific evaluation of critical nodes and enhance the reliability of subsequent cascading failure simulations. Two capacity parameters are introduced to analyze the nonlinear behavior between network node load and capacity, and an optimal recovery strategy is proposed. This strategy prioritizes the recovery of critical nodes, thereby minimizing the overall probability of network failure. Simulations were conducted under both random failure and deliberate attack scenarios, comparing the proposed strategy with random recovery and betweenness-priority recovery strategies to identify the optimal recovery approach. The experiments showed that the optimal recovery strategy significantly enhanced the network’s survivability and recovery efficiency, allowing for the restoration of basic network functions in the shortest possible time and reducing the impact of cascading failures. By integrating the operability and uncertainty of real-world command and control networks, this method improved the network’s recovery capability and overall stability in the face of cascading failures through scientific evaluation and strategy optimization.

Blood-spinal cord barrier in spinal cord injury: a scientific review based on own experimental trial

Objective. To analyze the mechanisms of the blood-spinal cord barrier permeability violation after spinal cord injury and to assess its impact on the development of secondary injuries, including those in the areas significantly remote from the epicenter of injury.Material and Methods. The article is an analysis of 45 publications supplemented by our own experimental data. The search for articles was conducted in databases such as PubMed, Scopus and Web of Science on the topic under study. Experimental data were obtained using confocal microscopy and bioluminescence detection on a rat spinal cord contusion injury model.Results. The problem of barrier disintegration in a region remote from the injury epicenter is considered. It is shown that spinal cord injury significantly increases the permeability of the blood-spinal cord barrier, which promotes enhanced transmigration of immune cells and release of cytotoxic molecules. The results of our own studies on a model of dosed contusion injury in the thoracic spinal cord of a rat show that the permeability of the barrier increases not only in the injury epicenter, but also along the entire length of the organ. This circumstance is especially significant for the lumbar spinal cord, where neural networks that are critical for the maintenance and restoration of motor function are localized.Conclusion. Potential causes of remote barrier disruption have been discussed, including the possible influence of damage biomarker molecules that travel from the injury epicenter to remote regions of the spinal cord via the bloodstream or cerebrospinal fluid. The promising clinical application of effective experimental approaches to contain barrier disruption and restore the blood-spinal cord barrier and the lack of translational research in this direction are highlighted.

Protective Effect of Aloe-emodin on Cognitive Function in Copper-loaded Rats Based on The Inhibition of Hippocampal Neuron Ferroptosis.

Aloe-emodin (AE), a monomer derived from traditional Chinese medicine, has demonstrated remarkable efficacy in the clinical management of cognitive disorders. Ferroptosis (FPT), a specialized form of programmed cell death, plays a critical role in the pathological progression of various cognitive diseases. This study explored the therapeutic potential of AE in a rat model of Wilson's disease cognitive impairments (WDCI) and examined whether these effects are mediated through the silencing information regulator 1 (SIRT1)-regulated FPT signaling pathway. Employing techniques, such as the Morris water maze (MWM), Hematoxylin & eosin (H&E) staining, Transmission electron microscopy (TEM), Immunofluorescence (IF), assessments of oxidative stress markers, and measurements of FPT-related protein levels, we evaluated the extent of SIRT1-mediated FPT and the therapeutic efficacy of AE. The findings from the WD copper-loaded rat model experiments revealed that MWM, H&E, TEM, and IF outcomes indicated AE's potential to promote the restoration of learning and memory functions, ameliorate hippocampal neuronal morphological damage, and preserve cell membrane integrity. Results from western blot (WB) and ELISA analyses demonstrated that AE markedly upregulated the expression of SIRT1, nuclear factor erythroid-2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SCL7A11), and glutathione peroxidase 4 (GPX4) proteins while simultaneously reversing the expression of oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), and reactive oxygen species (ROS). Consequently, we posit that AE may attenuate WD copper-loaded rat model hippocampal neuronal FPT by activating the SIRT1-mediated signaling pathway. These findings suggested that AE mitigates WD copper-loaded rat model hippocampal neuronal damage through the activation of SIRT1-mediated FPT, thereby presenting a valuable candidate Chinese herbal monomer for the clinical treatment of WDCI.

Deficient functional wound closure as measured by elevated trans-epidermal water loss predicts chronic wound recurrence: An exploratory observational study

A single-center, prospective, observational pilot study was performed to evaluate wound healing endpoint and recurrence by measuring transepidermal water loss (TEWL) post-closure at the site of wound repair. Patients with clinically-defined chronic wounds (such as pressure ulcers, diabetic ulcers, and trauma wounds) who visited the Plastic Surgery outpatient department or were in-patients at the All India Institute of Medical Sciences, Rishikesh, India, and were referred for chronic wound management, were enrolled. Non-invasive point-of-care TEWL measurements were obtained, from closed wound-site and contralateral healthy skin site, starting from confirmation of closure (post-closure, V0) continuing every 2 weeks for a maximum of five visits or until the wound recurred. Statistical analyses of the data involved logistic regression and likelihood ratio chi-square tests to assess differences in TEWL at visit 0 (V0) between the closed wound site and reference skin, with the TEWL score as the sole predictor of recurrence. Of the 72 subjects that completed the study, 44 (61%) showed no recurrence and 28 (39%) had wounds that recurred over a period of 12 weeks. A significant association was found between the V0 (post-closure) TEWL score and the odds of wound recurrence, both in univariate analysis (OR [95%CI] = 1.26[1.14,1.42] (p < 0.001) and after adjusting for covariates in multivariable analysis (OR [95%CI] = 1.34[1.19,1.61] (p < 0.001). The likelihood ratio chi-square analysis demonstrated that the V0 TEWL score is a significant universal predictor of recurrence across all wound types studied. Cases of closed wounds with subsequent recurrence showed an overall higher post-closure V0 TEWL score, compared to those who did not have a wound recurrence, across visits. The TEWL score cut-off value predictive of recurrence was 24.1 g.m–2.h–1 (AUC = 0.967). The outcome of this pilot study on a wide range of chronic wounds leads to the hypothesis that post-closure TEWL at the site of wound healing is a reliable biomarker of wound recurrence. It also raises the question whether the clinical endpoint of wound closure should include re-establishment of skin barrier function as additional criterion. The current standard of care wound closure endpoint calls for re-epithelialization of the wound with no discharge for two consecutive weeks disregarding the functional parameter of restoration of skin barrier function at the wound-site.

PERCUTANEOUS RELEASE OF THE MEDIAL COLLATERAL LIGAMENT DURING KNEE ARTHROSCOPY

The complete visualisation of the internal joint space is crucial for effective knee arthroscopy. However, limited access to certain areas can lead to complications, including cartilage damage. Percutaneous partial release of the medial collateral ligament has been shown to effectively widen the medial compartment of the joint. Objective. This study aimed to determine the effect of percutaneous release of the medial collateral ligament on the postoperative period and restoration of knee joint function. Methods. The patients were divided into two groups: the study group (n = 32) and the comparison group (n = 36). T he study group underwent partial resection of the medial meniscus in combination with percutaneous partial release of the medial collateral ligament, while the comparison group underwent only partial removal of the medial meniscus without widening the medial joint gap. The assessment included pain, functional recovery according to the Tegner Lisholm scale, and the possibility of developing medial instability. Results. The analysis of VAS scores showed a significant reduction in pain in both groups over time. However, there was no significant difference in pain intensity between the two groups during the study. According to the Tegner Lysholm scale, there was a statistically significant improvement in the functional status of patients 6 months after surgery compared to preoperative values in both the study group (p = 0.0034) and the control group (p = 0.0071). However, there was no statistically significant difference between the groups on t he s ame s cale ( p = 0 .871). The study g roup s howed a s light increase in valgus deviation of the tibia (no more than 5o) in 14 (43.75%) patients during the valgus stress test performed on days 7–10 postoperatively. However, after 6 weeks, none of the patients reported any subjective instability or weakness of the knee joint. Therefore, it can be concluded that the procedure was successful. Conclusion. Percutaneous release of the medial collateral ligament to widen the medial aspect during knee arthroscopy has no effect on the postoperative period or the results of partial removal of the medial meniscus.

OSSEOINTEGRATIVE PROSTHETICS: OPPORTUNITIES, CHALLENGES, AND PROSPECTS FOR ITS APPLICATION IN THE REHABILITATION OF PATIENTS WITH AMPUTATED LIMBS (LITERATURE REVIEW)

Rehabilitation of patients with amputated limbs is a pressing medical and social issue in modern society. A novel method for partial restoration of limb function is osseointegrative prosthetics. Its main advantage lies in the fact that the implant allows mechanical loads and forces to be transmitted directly to the bone, whereas in traditional prostheses, they mainly act on soft tissues. Despite nearly 30 years of experience with osseointegrative implants globally, these technologies have not yet been implemented in either scientific or clinical practice in Ukraine. Objective. To conduct a literature review of the global practical experience with the use of osseointegrative prosthetics in patients with amputations and to identify its main features, advantages, and disadvantages. Methods. The information search was performed in the bibliographic databases PubMed, Scopus, and Google Scholar. Results. The analysis of literature sources allowed us to distinguish the main types of osseointegrative implants, which differ in terms of design, materials, and surgical techniques: either single-stage or two-stage procedures, and fixation by threading or press-fitting. The rehabilitation period ranges from 6 months to 2 years. Within the first two years, certain complications such as bone infections and skin inflammation should be expected. Hфowever, most of these pathological conditions can be effectively managed. Conclusions. Successful fixation of osseointegrative implants requires optimizing the patient’s bone, the prosthetic surfaces, and the ‘skin-implant’ interface. The implementation of these technologies requires multidisciplinary teams of specialists, including physicians, engineers, and rehabilitation experts. Osseointegrative implants significantly enhance patients’ functional abilities and quality of life, opening up greater opportunities for the use of bionic and robotic prosthetics.

Hybrid bionic control system for prostheses: a review

The legs and hands are the most susceptible to loss and this is due to the fact that they are prominent external organs in the human body. With increasing disasters, accidents, wars and diseases the loss of limbs is increasing, making the individual restricted in freedom and movement and pursuing to find alternatives to improve the individual's life is extremely important. Modern bionic prostheses are the best alternatives to replace amputated ones to perform both aesthetic and functional tasks. On this basis and by analyzing the most common and used methods in prosthetics management as the electroencephalography (EEG), electromyography (EMG), and functional near- infrared spectroscopy (fNIRS) methods, knowing their advantages and disadvantages, comparing them and documenting their results from the outputs of literature and previous experimental studies, whether in individual use or hybrid use.In the light of these data, this article highlights the most common technologies and considers their superiority and insuperiority, which can be suitable for the formation of a hybrid bionic control system for prostheses or rehabilitation and restoration of lost functions. Based on the most important studies that have dealt with these technologies whereas individually or in their hybrid state. In addition, this article provides an encouraging outlook for those interested in scientific research to research, compare, identify and characterise superior hybrid systems related to exoskeletal control systems and in particular prostheses.

Fixed Prosthodontic Rehabilitation of a Patient with Cleidocranial Dysplasia: A Case Report

Introduction Cleidocranial Dysplasia (CCD) is a rare congenital disease characterized by skeletal and dental anomalies. Clinical findings of CCD patients include low facial height, pseudoprognathism, unerupted teeth, an excessive deep bite, chewing difficulties, and unsatisfied dentofacial appearance. These patients’ dental treatments present a substantial challenge. Case Representation This case report describes the prosthodontic treatment of a 29-year-old male CCD patient using porcelain-fused-to-metal restorations. The avoidance of a surgical procedure serves to minimize the potential for complications and expedites the attainment of outcomes with greater celerity. Throughout the follow-up period of 1 year, the patient maintained good periodontal health. The restoration of masticatory function and enhancement of facial esthetics were successfully achieved and the patient expressed a high degree of satisfaction with the outcome of the treatment. Conclusion The use of fixed prostheses in CCD patients is a treatment modality that resolves many of the issues caused by the surgical approach.

On the issue of maintaining a balance of private and public interests in satisfying creditors’ claims in bankruptcy proceedings

The article analyzes the problems of satisfying creditors’ claims in bankruptcy proceedings. In the context of a conflict of interests of creditors caused by insufficient property of an insolvent debtor, the search for an optimal model for satisfying their claims was carried out. Common conflict situations arising between pledgees and authorized bodies have been identified. For example, in cases of satisfaction of claims for mandatory payments secured by the seizure of a taxpayer’s property. The tax authorities, as current creditors, also file claims for payment of income tax, property tax and land tax. The legal positions of the Constitutional Court of the Russian Federation are analyzed. It is concluded that it is necessary to eliminate the imbalance of interests of collateral creditors and authorized bodies, and restoration of the security function of the pledge.

12343 Cardiac Function Recovery Following Left Adrenalectomy For A Pheochromocytoma With Ectopic ACTH Syndrome

Abstract Disclosure: T.D. Williams: None. D. Lovre: None. R.C. Galagan: None. Background: Pheochromocytoma and Cushing’s Syndrome are implicated in Non-ischemic Cardiomyopathy/Heart Failure with reduced Ejection Fraction (NICM/HfrEF) due to catecholamine induced hypertension and cardiomyocyte toxicity. Subsequent hypoxia and calcium overload in cardiomyocytes results in oxidative stress and cell death. Excess cortisol secretion increases angiotensin II, causing hypertrophy. Subsequent increases in atrogin I lead to myo-fibrinolysis and fibrosis. We present a patient with NICM/HFrEF due to both catecholamine excess and ectopic ACTH syndrome from an adrenal pheochromocytoma. Following adrenalectomy, systolic cardiac function returned to normal. Clinical Case A 42-year-old female was referred to endocrinology after a hypertensive emergency concurrent with NSTEMI, NICM, and HFrEF (EF 45%). Initial work up revealed: Troponin I 0.49 ng/ml; (0 - 0.04 ng/ml), Na+ 140 mmol/L; (136 - 144 mmol/L), K+ 2.3 mmol/L; ​​(3.7 - 5.2 mmol/L), CO2 41 mmol/L; (23 - 29 mmol/L), Glucose 53 mg/dL; (64 - 100 mg/dL), Cortisol 57.2 ug/dL; (5 - 25 ug/dL), ACTH 363.7 pg/mL; (7.2 - 63.3 pg/mL). She failed both 1 mg and 8 mg overnight dexamethasone suppression tests: 0800 cortisol 48.5 ug/dL (&amp;lt; 1.8 ug/dL) &amp; 56.8 ug/dL (&amp;gt; 50% decrease in baseline cortisol level of 57.2 ug/dL) consistent with ectopic ACTH syndrome. Elevated plasma normetanephrine 0.98 nmol/L; (0 - 0.89 nmol/L) and chromogranin A 250 ng/mL; (0 - 103 ng/mL) suggested a neuroendocrine tumor. Pituitary MRI revealed a normal pituitary gland. Abdominal MRI detected a 3.6 x 2.5 cm left adrenal nodule and PET/CT CU-64 showed increased activity (Krenning 4) consistent with a pheochromocytoma. Notwithstanding Ketoconazole (200 mg/day) for 7 months, her EF fell to a low of 15-20%. A left adrenalectomy was performed and post-op 0800 cortisol was 12.3 ug/dL (6.0 - 26.0 ug/dL). Oral hydrocortisone was initiated at 20 mg QAM/10 mg QPM for steroid withdrawal syndrome, tapered over 8 months and withdrawn when a cosyntropin stimulation test 60-min cortisol was 19.3 ug/dL; (&amp;gt;18.0 ug/dL). Eleven months post op, her 0800 cortisol was 8.8 ug/dL and ACTH 27.4 pg/mL. One month post-op, TTE showed EF: 15-20%, six months post-op EF: 25-30%, eight months post-op EF: 35-40% and 15 months post-op EF was normal at 50%. Her heart failure symptoms resolved, and her activity returned to normal. Conclusion This case illustrates a remarkable restoration of cardiac function following resection of a pheochromocytoma. Our patient's case is unique due to the restoration of cardiac function despite the dual impact of excessive catecholamines and cortisol. Our patient’s clinical course contributes to an evolving understanding of cardiomyopathy associated with pheochromocytoma and ectopic ACTH syndrome and highlights the potential for cardiomyopathy reversal with targeted endocrine surgical and medical interventions. Presentation: 6/1/2024

Structural elucidation of a Acanthopanax senticosus polysaccharide CQ-1 and its hepatoprotective activity via gut health regulation and antioxidative defense

Acanthopanax senticosus has proven health benefits, particularly for liver damage. The objective of this study was to elucidate the protective effects and the underlying mechanisms of action of A. senticosus against metabolic dysfunction-associated fatty liver disease (MAFLD). A novel homogeneous water-soluble polysaccharide, CQ-1, was successfully isolated and purified from A. senticosus root. The main chain structure of CQ-1 was identified as →2)-α-L-Rha-(1 → 4)-α-D-GalAp-(1 → 6)-β-D-Galp-(1→. Additionally, branched chains comprising an arabinosyl residue, galactosyl residue, and galacturonic acidic residue were identified as being attached to →2,4)-α-L-Rha-(1→, →3,6)-β-D-Galp-(1→, and →3,4)-α-D-GalAp-(1→, respectively. CQ-1 exhibited antioxidant and prebiotic activities in vitro. CQ-1 increased antioxidant capacity and reduced serum pro-inflammatory cytokines in mice. Additionally, CQ-1 has been shown to enhance the diversity and composition of the gut microbiota, thereby facilitating the restoration of gut function. These include improving intestinal barrier function and increasing short-chain fatty acid levels in mice. Our study has shown that CQ-1 has a hepatoprotective effect in MAFLD mice, and we have proposed that CQ-1 may be a promising strategy for the treatment of MAFLD.

8071 Prevention Of Acute Kidney Injury By Reducing Mitochondrial Dysfunction In Diabetic Mice

Abstract Disclosure: M. Kim: None. C. Oh: None. A. Khang: None. J. Jeon: None. I. Lee: None. Background: Acute Kidney Injury (AKI) significantly contributes to the pathogenesis of diabetic kidney disease, often exacerbating chronic kidney disease (CKD) and accelerating the need for dialysis. Mitochondrial dysfunction, induced by an increase in reactive Oxygen Species (ROS) and inflammation, plays a crucial role in AKI. This study investigates the prevention of AKI by reducing mitochondrial dysfunction through pyruvate dehydrogenase kinase (PDK) inhibition in an ischemia-reperfusion (IR)-induced AKI model using streptozotocin (STZ)-induced diabetic mice. Methods: We utilized an IR-induced AKI model in STZ-induced diabetic C57BL6/J mice, subjecting them to IR by clamping both renal pedicles. Mitochondrial function tests, cellular apoptosis, and inflammatory markers were evaluated in NRK-52E cells and mouse primary tubular cells after hypoxia and reoxygenation using a hypoxia workstation. Results: In diabetic mice experiencing AKI following IR injury, there was a significant increase in pyruvate dehydrogenase E1α (PDHE1α) phosphorylation. This correlated with a notable increase in mitochondrial damage - TEM images of mice with IR-induced kidney injury revealed distension, loss of cristae, and fragmentation of the mitochondria. We also observed a decrease in oxygen consumption rate (OCR) accompanied by increased ROS, as well as increased production of inflammatory markers. Remarkably, the pan-PDK inhibitor, sodium dichloroacetate (DCA), mitigated apoptosis, attributable to the reduction of PDHE1α phosphorylation levels as well as normalized mitochondrial morphology and function. DCA treatment lessened oxidative stress and decreased the production of inflammatory markers following IR-induced AKI or hypoxia-reoxygenation injury. Conclusion: Restoration of mitochondrial function by DCA effectively alleviated renal injury by decreasing ROS production and inflammation, highlighting its critical role in IR-mediated damage. These results suggest another potential target for renal protection during AKI; therefore, the prevention of acute kidney injury through the inhibition of PDK could be a promising therapeutic approach for treating Diabetic Kidney Disease (DKD). Presentation: 6/1/2024

Optogenetic targeting of cortical astrocytes selectively improves NREM sleep in an Alzheimer’s disease mouse model

Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by memory impairments and distinct histopathological features such as amyloid-beta (Aβ) accumulations. Alzheimer’s patients experience sleep disturbances at early stages of the disease. APPswe/PS1dE9 (APP) mice exhibit sleep disruptions, including reductions in non-rapid eye movement (NREM) sleep, that contribute to their disease progression. In addition, astrocytic calcium transients associated with a sleep-dependent brain rhythm, slow oscillations prevalent during NREM sleep, are disrupted in APP mice. However, at present it is unclear whether restoration of circuit function by targeting astrocytic activity could improve sleep in APP mice. To that end, APP mice expressing channelrhodopsin-2 (ChR2) targeted to astrocytes underwent optogenetic stimulation at the slow oscillation frequency. Optogenetic stimulation of astrocytes significantly increased NREM sleep duration but not duration of rapid eye movement (REM) sleep. Optogenetic treatment increased delta power and reduced sleep fragmentation in APP mice. Thus, optogenetic activation of astrocytes increased sleep quantity and improved sleep quality in an AD mouse model. Astrocytic activity provides a novel therapeutic avenue to pursue for enhancing sleep and slowing AD progression.

Differential effect of plakoglobin in restoring the tumor suppressor activities of p53-R273H vs. p53-R175H mutants.

The six most common missense mutations in the DNA binding domain of p53 are known as "hot spots" and include two of the most frequently occurring p53 mutations (p53-R175H and p53-R273H). p53 stability and function are regulated by various post-translational modifications such as phosphorylation, acetylation, sumoylation, methylation, and interactions with other proteins including plakoglobin. Previously, using various carcinoma cell lines we showed that plakoglobin interacted with wild-type and several endogenous p53 mutants (e.g., R280K, R273H, S241F, S215R, R175H) and restored their tumor suppressor activities in vitro. Since mutant p53 function is both mutant-specific and cell context-dependent, we sought herein, to determine if plakoglobin tumor suppressive effects on exogenously expressed p53-R273H and p53-R175H mutants are similarly maintained under the same genetic background using the p53-null and plakoglobin-deficient H1299 cell line. Functional assays were performed to assess colony formation, migration, and invasion while immunoblotting and qPCR were used to examine the subcellular distribution and expression of specific proteins and genes that are typically regulated by or regulate p53 function and are altered in mutant p53-expressing cell lines and tumors. We show that though, plakoglobin interacted with both p53-R273H and p53-R175H mutants, it had a differential effect on the transcription and subcellular distribution of their gene targets and their overall oncogenic properties in vitro. Notably, we found that plakoglobin's tumor suppressive effects were significantly stronger in p53-R175H expressing cells compared to p53-R273H cells. Together, our results indicate that exploring plakoglobin interactions with p53-R175H may be useful for the development of cancer therapeutics focused on the restoration of p53 function.

Rational design, synthesis, and biophysical characterization of a peptidic MDM2-MDM4 interaction inhibitor

In recent years, the restoration of p53 physiological functions has become an attractive therapeutic approach to develop novel and efficacious cancer therapies. Among other mechanisms, the oncosuppressor protein p53 is functionally regulated by MDM2 through its E3 ligase function. MDM2 promotes p53 ubiquitination and degradation following homodimerization or heterodimerization with MDM4. Recently, we discovered Pep3 (1, Pellegrino et al., 2015), a novel peptidic inhibitor of MDM2 dimerization able to restore p53 oncosuppressive functions both in vitro and in vivo. In this work, we were able to identify the key interactions between peptide 1 and MDM2 RING domain and to design peptide 2, a truncated version of 1 that is still able to bind MDM2. Integrating both computational and biophysical techniques, we show that peptide 2 maintains the conserved peptide 1-MDM2 interactions and is still able to bind to full-length MDM2.

CLINICAL CASE OF A NEW METHOD FOR SURGICAL TREATMENT OF HILL-SACHS REVERSAL FRACTURE IN OLD-ENGINED POSTERIOR SHOULDER DISLOCATION.

The article presents a clinical case in which the use of a new method of surgical treatment of a HILL-SACHS type reversal fracture in chronic posterior shoulder dislocation is considered. In this clinical case, we proposed an operational-biomechanical theory, the main goal of which is surgical treatment of a HILL-SACHS reversal fracture with stabilization of the shoulder joint by moving the tendon of the long head of the biceps to the impression zone and fixing it with anchors. The outcome of this clinical case is the absence of clinical symptoms of instability of the shoulder joint and restoration of function of the shoulder joint in the late postoperative period.

ULTRASOUND DIAGNOSIS OF THE RENAL ARTERY STENOSIS IN A TRANSPLANTED KIDNEY IN THE EARLY POSTOPERATIVE PERIOD

In this clinical case, stenosis of a renal artery of transplant was detected in time by angiography using dynamic Doppler ultrasound control. The chosen treatment method allowed the restoration of arterial patency and thus renal graft function in the shortest possible time and with minimal trauma. However, due to the high risk of restenosis in the plastic area, continuous dynamic ultrasound monitoring and monitoring of the patient's creatinine level are required. The purpose of this presentation is to present a case of early detection of a postoperative complication by Doppler ultrasound, which made it possible to prevent vascular dysfunction, often leading to loss of the renal graft. Materials and Methods. In this article, we report a case of timely detection of renal artery stenosis by ultrasound in a patient, followed by confirmation by angiography and restoration of renal artery and graft function by endovascular balloon angioplasty. All major hemodynamic changes in Doppler ultrasound parameters characteristic of renal artery stenosis are described in this article. Results. Dynamic Doppler ultrasound monitoring and angiography allowed early detection of the described complication of renal transplantation. The optimal choice of treatment tactics allowed the restoration of arterial patency and renal graft function in the shortest possible time, thus preventing graft rejection. Conclusion. Our clinical case demonstrates the importance of the monitor in the assessment of renal perfusion. The outcome of kidney transplantation largely depends on the successful resolution of these issues, which determines the relevance.

Patient-Reported Quality of Life for Osteoradionecrosis Reconstruction in the Head and Neck: A Longitudinal Framework and Risk Factors.

Osteoradionecrosis (ORN) is an aggressive sequela of head and neck cancer, treatment of which focuses on functional restoration and quality-of-life (QoL). This study aims to identify risks for poor QoL in ORN reconstruction and build a chronologic, longitudinal framework for QoL. A prospective database of reconstructions performed by the senior author was reviewed from 2015-2023. QoL metrics (University of Washington [UWQoL]v4) were prospectively administered prior to surgery, one year post-operatively, and each yearly follow-up. 56 ORN patients were included (average 58.2years, mean 6,412Gy radiation). Reconstruction commonly was achieved with the fibula(55.4%) and anterolateral-thigh flaps(37.5%). The total complication rate was 23.2%, median 10.7mo post-operatively.Both "health-related QoL in comparison with prior to cancer diagnosis" (62.5 vs 43.5;p=0.030) and "Overall QoL during the past 7-days" (50.5 vs 41.7;p=0.029) were higher post-ORN reconstruction than before. Physical-QoL was higher pre-cancer reconstruction (79.0) than prior to ORN reconstruction (50.6;p<0.001) and following reconstruction (52.5;p=0.001). Social-emotional function was higher following ORN reconstruction compared to pre-reconstruction (68.7 vs 59.6;p=0.010).On multi-variate analysis, both post-operative social-emotional and physical function were impacted by betelnut use (p=0.038;p=0.025). Poor improvement in QoL from pre to post-ORN reconstruction were affected by maxilla involvement (p=0.048), fistula (p=0.004), and hardware issues (p=0.001). Our longitudinal experience trended decline in QoL at ORN diagnosis with gradual improvement following reconstruction, with eventual social-emotional, pain, anxiety, chewing, and global-QoL significantly improved following surgery. Betelnut was a risk factor for poor post-operative QoL. Maxillary involvement, post-op fistula and hardware issues were risks for non-improvement in QoL.

ID: 344560 Spinal cord stimulation as a dual-purpose treatment for Spinal Cord Injury, Pain and Functional Restoration

ID: 344560 Spinal cord stimulation as a dual-purpose treatment for Spinal Cord Injury, Pain and Functional Restoration