Simulation-Based Research on Phytoconstituents of Embelia ribes Targeting Proteins with Pathophysiological Implications in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a heterogeneous inflammatory disease with an autoimmune origin and an incompletely elucidated pathophysiological mechanism. RA pharmacotherapy is based on chemically or biologically active substances that provide clinical alleviation and remission, but the disease is still incurable. As a result, there remains a need for significant therapeutic development, and adjuvant therapies may play an essential role in the search for novel RA treatment strategies. The aim of the present study was to investigate potential phytocompounds and phytocompound derivates as RA treatment agents, using in silico methodologies. In this regard, five phytoconstituents identified in different structures of Embelia ribes were evaluated by in silico methods for their potential action on target proteins of therapeutic interest in RA. The methodology involved identifying the phytocompound with the highest binding toward the target protein via molecular docking using AutoDock Vina 1.5.7, followed by a ligand-based virtual screening based on the structure of the most promising phytocompound using SwissSimilarity. This process led to the identification of ligands that are not currently utilized in medical practice, but that might have the potential to be used in the management of RA after further extensive experimental endorsements. ZINC000004024651 showed the highest binding affinity for the Bruton's tyrosine kinase protein, followed by ZINC000000434197 for p38 mitogen-activated protein kinases, ZINC000087606977 for interleukin-1 receptor-associated kinase 4, and ZINC000014728393 for matrix metallopeptidase 9, the latter two showing higher affinity than the co-crystallized compound. The relatively high affinities to target proteins and the pharmacokinetic data obtained by in silico studies using SwisADME suggest a first step for the inclusion of promising new compounds in various more advanced studies, leading to the evaluation of efficacy and safety profiles.

Novel Potential Janus Kinase Inhibitors with Therapeutic Prospects in Rheumatoid Arthritis Addressed by In Silico Studies.

Rheumatoid arthritis (RA) is a debilitating autoimmune disorder with an inflammatory condition targeting the joints that affects millions of patients worldwide. Several unmet needs still need to be addressed despite recent improvements in the management of RA. Although current RA therapies can diminish inflammation and alleviate symptoms, many patients remain unresponsive or experience flare-ups of their ailment. The present study aims to address these unmet needs through in silico research, with a focus on the identification of novel, potentially active molecules. Therefore, a molecular docking analysis has been conducted using AutoDockTools 1.5.7 on Janus kinase (JAK) inhibitors that are either approved for RA or in advanced phases of research. The binding affinities of these small molecules against JAK1, JAK2, and JAK3, which are target proteins implicated in the pathophysiology of RA, have been assessed. Subsequent to identifying the ligands with the highest affinity for these target proteins, a ligand-based virtual screening was performed utilizing SwissSimilarity, starting with the chemical structures of the previously identified small molecules. ZINC252492504 had the highest binding affinity (-9.0 kcal/mol) for JAK1, followed by ZINC72147089 (-8.6 kcal/mol) for JAK2, and ZINC72135158 (-8.6 kcal/mol) for JAK3. Using SwissADME, an in silico pharmacokinetic evaluation showed that oral administration of the three small molecules may be feasible. Based on the preliminary results of the present study, additional extensive research is required for the most promising candidates to be conducted so their efficacy and safety profiles can be thoroughly characterized, and they can become medium- and long-term pharmacotherapeutic solutions for the treatment of RA.

Application of Robotic Recovery Techniques to Stroke Survivors-Bibliometric Analysis.

Stroke is a significant disability and death cause worldwide and is conventionally defined as a neurological impairment relating to the intense focal harm of the central nervous system (CNS) by vascular causative components. Although the applicability of robotic rehabilitation is a topic with considerable practical significance because it has produced noticeably higher improvements in motor function than regular (physical and occupational) therapy and exempted the therapists, most of the existing bibliometric papers were not focused on stroke survivors. Additionally, a modular system is designed by joining several medical end-effector devices to a single limb segment, which addresses the issue of potentially dangerous pathological compensatory motions. Searching the Web of Science database, 31,930 papers were identified, and using the VOSviewer software and science mapping technology, data were extracted on the most prolific countries, the connections between them, the most valuable journals according to certain factors, their average year of publication, the most influential papers, and the most relevant topical issues (bubble map of term occurrence). The most prolific country in the analyzed field and over the entire period evaluated (1975-2022) is the United States, and the most prolific journal is Neurorehabilitation and Neural Repair, observing a marked increase in the three periods of scientific interest for this field. The present paper assesses numerous scientific publications to provide, through statistical interpretation of the data, a detailed description of the use of robotic rehabilitation in stroke survivors. The findings may aid scientists, academics, and clinicians in establishing precise goals in the optimization of the management of stroke survivors via robotic rehabilitation, but also through easier access to scientifically validated literature.

The Outcomes of Robotic Rehabilitation Assisted Devices Following Spinal Cord Injury and the Prevention of Secondary Associated Complications.

Spinal cord injuries (SCIs) have major consequences on the patient's health and life. Voluntary muscle paralysis caused by spinal cord damage affects the patient's independence. Following SCI, an irreversible motor and sensory deficit occurs (spasticity, muscle paralysis, atrophy, pain, gait disorders, pain). This pathology has implications on the whole organism: on the osteoarticular, muscular, cardiovascular, respiratory, gastrointestinal, genito-urinary, skin, metabolic disorders, and neuro-psychic systems. The rehabilitation process for a subject having SCIs can be considered complex, since the pathophysiological mechanism and biochemical modifications occurring at the level of spinal cord are not yet fully elucidated. This review aims at evaluating the impact of robotic-assisted rehabilitation in subjects who have suffered SCI, both in terms of regaining mobility as a major dysfunction in patients with SCI, but also in terms of improving overall fitness and cardiovascular function, respiratory function, as well as the gastrointestinal system, bone density and finally the psychosocial issues, based on multiple clinical trials, and pilot studies. The researched literature in the topic revealed that in order to increase the chances of neuro-motor recovery and to obtain satisfactory results, the combination of robotic therapy, a complex recovery treatment and specific medication is one of the best decisions. Furthermore, the use of these exoskeletons facilitates better/greater autonomy for patients, as well as optimal social integration.

Highlighting the Benefits of Rehabilitation Treatments in Hip Osteoarthritis.

Background and objectives: Due to its frequency and possible complications, hip arthrosis or hip osteoarthritis (hip OA) has a high social impact, its advanced stages eventually leading to irreversible lesions involving major complications or surgery. In the early stages, conservative treatment plays a key role in the prophylaxis of complications and in slowing down the degenerative process. The association between an appropriate drug therapy (DT) and a rehabilitation treatment (RT)­including individualized physical therapy (PT) and adapted occupational therapy (OT)­provides good results. Our objective was to highlight the benefits of associating RT with DT in patients with hip OA. Materials and Methods: An observational follow-up study was conducted between 2018−2021, which included 100 patients with hip OA divided into two groups: the study group­group A (50 subjects who complied with RT) and the control group­group B (who did not comply with RT). To evaluate them, the evolution of the Lequesne hip index (LHI), Tinetti test (TT) and the hip joint mobility: flexion (FH) and abduction (AH) were monitored before the beginning of the study (T0) and after one-year (T1) for each patient. The mean values of the parameters, the standard deviations, the frequency intervals, as well as the tests of statistical significance were calculated using the Student method (t-test) and χ2, ANOVA (Bonferroni) being used to compare the means. Results: Compared to the evolution of group B, improvements were observed in group A, as follows: in LHI group A (p = 0.023) vs. group B (p = 0.650); in TT group A (p = 0.011) vs. group B (p < 0.001); in FH group A (p = 0.001) vs. group B (p = 0.025); in AH group A (p = 0.001) vs. group B (p < 0.001). BMI changes were non-significant in both groups A (p = 0.223) and B (p = 0.513). Evaluating group A, the most significant improvements of the studied parameters were observed in the age group 41−50 years. Conclusions: The study reveals the benefits of combining RT with DT in patients with especially early-stage hip OA, aged up to 50 years old.

Therapeutic approaches in the management of knee osteoarthritis (Review).

Osteoarthritis (OA) is a common, frequently met degenerative disease, that generates pain and decreasing functionality; risk of suffering from this disorder increases with ageing. Being a complex disease, treatment is often difficult due to complications. Knee OA therapy demands a strategy that specialists agree with in considering the clinical symptoms and the disease evolution. The initial management of its treatment should be conservative requiring both a pharmacological and a non-pharmacological approach. If this conservative, noninvasive therapy fails, the surgical approach is discussed. The present review focused on the assessment of therapy choices for patients with knee OA, in order to reduce pain and enhance functionality and knee range of motion, underlying benefits and advantages for each choice. Existing data of available treatment for knee OA, both surgical and nonsurgical were analyzed, focusing on the latest results, indications, developments, and level of evidence provided by the literature in the topic.

Highlighting the advantages and benefits of cementless total knee arthroplasty (Review).

In the field of orthopedic surgery, cemented total knee arthroplasty (TKA) is considered to be one of the gold standards. However, there are categories of patients (i.e., obese and morbidly obese patients, younger than 65 years old) among whom cemented TKA has however a high failure rate. Moreover, the frequency of using uncemented TKA is increasing due to the potential benefits of long-term biological fixation, being an innovative field that addresses a new generation orthopedic surgical treatment which is more suitable for young patients who have good bone quality (good to very good, in terms of density). The survival rates and functional results of the latest generation of cementless TKAs may be similar to functional results and survival rates of cemented prosthesis. In conclusion, this review-type article can be considered a powerful database, extremely informative, dense, and focused on the topic mentioned above, in the interest of all medical professionals and all interested individuals.

Benefits of Combining Physical Therapy with Occupational Therapy in Hip Arthroplasty.

(1) Background: Hip arthroplasty (HA) is a surgery that replaces the damaged hip joint with an artificial implant called a hip prosthesis. The increase in life expectancy correlated with the population aging level, to which the increase in the number of prosthetic interventions among the young population is added, translates to the imperative need to analyze the quality of life beyond the immediate postoperative period. Strict adherence to an individualized rehabilitation program (IRP), and adapted to each patient, is followed by an improved quality of life. The main goal is the recovery of the patient with HA. This study was aimed to demonstrate that an IRP, represented by physical therapy associated with occupational therapy, improves the quality of life of patients with HA; (2) Methods: In this study, conducted between 2019 and 2021, 50 patients with HA were divided into two groups: study group-group A (25 subjects compliant with the IRP) and control group-group B (25 subjects, non-compliance with the IRP). To evaluate the two study groups, we monitored the evolution of the modified Harris hip score (mHHS) in both hips (arthroplasty hip (AH), contra lateral hip (CH)), for four months, respectively 30 days before the surgery (T0) and at 90 days after the surgery (T1); (3) Results: We notice significant differences in mHHS values at 90 days-T1 after surgery, both on AH in favor of subjects from group A vs. group B (p = 0.030) and on CH, where mHHS values were statistically higher in group A compared to group B (p < 0.001). The results of our study outline at T1 moment, both on the AH (p = 0.030) and on the CH (p < 0.001), the fact that mHHS values were statistically higher in patients included in group A compared to group B. In terms of the results for mHHS, comparing AH with CH, it is noted that the number of subjects who had a good or excellent mHHS result in group A versus group B is statistically significant in the case of CH (group A: 23 (92%) vs. group B: 11 (44%), p = 0.039); (4) Conclusions: The study reveals clear advantages of HA in both hips, both in subjects who complied with the IRP and those who did not comply; the higher therapeutic benefits of IRP are outlined at the level of CH compared to AH; in patients who comply with the IRP, the mHHS parameters that have improved in both CH and AH are pain, leaning, and shoes and socks activities; in addition, limping was reduced in CH.

Orthopedic surgery approach with uncemented metallic prosthesis in knee osteoarthritis increases the quality of life of young patients.

Osteoarthritis is mainly located in the knee area. It is an important concern related to the population health, determined by the influence on the quality of life of patients. Total knee arthroplasty (TKA) with uncemented fixation is among the most encountered procedures performed in patients of a younger age. The present study investigated the response of patients (quality of life, mobility and pain management) with titanium/hydroxyapatite-coated implants with polyethylene inserts. A total of 57 patients with knee arthroplasty were studied with an average age of 54.1±4.9 years and 57.8% were females. The present study focused on the following aspects: The components of such a prosthesis and the way they contribute to a physiological fixation/recovery; how the implant surgery is performed; the clinical and demographic characteristics of the patients; postoperative pain assessment in different types of movement; the management of the movement capacity 1 year after the surgery; and complications that may occur. One year after the surgery, these patients reported pain release, considerably favorable results in every-day activities, and good mobility (capable of using the car, rising from the bed or standing). Knowledge and accurate observation of the correct steps in performing this surgery and the role of the components of the prosthesis can lead to favorable therapeutic outcomes for patients with knee osteoarthritis.

Clinical, Pathological and Microbiological Evaluation of Diabetic Foot Syndrome.

Background and objectives: Diabetic foot ulcer (DFU) is one of the serious complications of diabetes, being related to frequent and long-term hospitalisation, reduced quality of life of the patient, amputations, a high rate of morbidity and mortality. The bacterial aetiology is complex, sometimes involving more than one pathogen, playing a major role in the infection prognosis and development of microbial resistance. This study evaluated the current state of the aetiology, clinical and pathological characteristics of DFU in a single diabetes centre in order to provide some specific measures to prevent it. Materials and Methods: This retrospective study was conducted on patients with diabetes mellitus (252 individuals diagnosed with DFU) between January 2018-December 2019. All participants were assessed based on their clinical characteristics, including complications of diabetes and pathological and microbiological evaluations. Results: The present research revealed that diabetic foot ulcer prevalence was higher in males than in females and higher in type 2 diabetic patients than in type 1 diabetic patients. The patients with diabetic foot ulcer were older, had a higher body mass index (BMI), longer diabetic duration and had more diabetic complications, such as retinopathy, diabetic polyneuropathy and diabetic kidney disease, than patients without diabetic foot ulceration. Conclusions: Taking into account all factors involved, including the aetiology and the antibiotic susceptibility pattern of these isolates, planning the suitable treatment options of patients is possible.