Janus kinase inhibitors versus tumor necrosis factor inhibitors in rheumatoid arthritis: meta-analytical comparison of efficacy and safety.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by persistent inflammation leading to progressively worse disability. Janus kinase (JAK) inhibitors and tumor necrosis factor (TNF) inhibitors are pivotal in RA treatment, yet their comparative efficacy remains underexplored. AIM: This study aimed to compare the efficacy and safety of JAK inhibitors and TNF inhibitors in treating RA using data from randomized controlled trials (RCTs). METHODS: A meta-analysis and outcomes analysis were based on results of the Health Assessment Questionnaire Disability Index (HAQ-DI), Clinical Disease Activity Index (CDAI), Visual Analogue Scale (VAS), and Patient Global Assessment Scale (PtGA) and other indices as incidences of venous thromboembolism (VTE) and malignancy. RESULTS: The JAK inhibitors caused a statistically significant improvement in the HAQ-DI score [MD = 0.08, 95% CI (0.03, 0.12), p = 0.0008] compared with the TNF inhibitors. However, no significant difference was observed between the two drug classes in the CDAI score [MD = - 2.03, 95% CI (- 9.27, 5.22), p = 0.58]. JAK inhibitors were associated with an increase in the VAS score [MD = 3.62, 95% CI (0.86, 6.38), p = 0.01], but there was no significant difference in the PtGA score [MD = 1.91, 95% CI (- 3.25, 7.08), p = 0.47]. CONCLUSION: JAK inhibitors demonstrated superior efficacy in improving the functional status and reducing the disease activity in RA patients compared with TNF inhibitors. Both drug classes exhibited comparable safety profiles for VTE and malignancies, though JAK inhibitors had a higher risk for thromboembolism.

Outcomes of Zone II Flexor Tendon Repair Under General Versus Wide Awake Local Anesthesia: A Randomized Controlled Trial.

PURPOSE: Wide awake local anesthesia no tourniquet (WALANT) is gaining popularity with flexor tendon repair. We hypothesized that results of zone II flexor tendon repair performed under WALANT would be superior to those performed under general anesthesia (GA). METHODS: A randomized controlled trial was conducted to compare results of repair of zone II flexor tendon lacerations under WALANT versus GA. Following sample size estimation, 86 digits were included and randomized into two groups. All surgeries were performed by a single surgeon using a six-stranded core stitch and running epitenon suture. All patients followed the same early active rehabilitation protocol. The primary outcome was recovery calculated using the Strickland and Glogovac criteria. Secondary outcomes included rupture rate, complication rate, and Disabilities of the Arm, Shoulder, and Hand (DASH) score. All outcomes were reported at the 6-month visit for all patients. RESULTS: Of the 86 digits, three were lost to follow-up. Analysis was performed on 43 digits in the WALANT group and 40 in the GA group. Demographic characteristics including age and sex were comparable in both groups. Rupture of the repair occurred in two digits in each of the WALANT and GA groups. An excellent or good outcome was achieved in 49% and 56% of the digits in the WALANT and GA groups, respectively. This difference was not statistically significant. DASH scores averaged 12.9 and 8.4 for the WALANT and GA groups, respectively. CONCLUSIONS: WALANT may not be superior to GA in regards function, rates of rupture, and patient-reported outcomes in repair of zone II flexor tendon lacerations. Surgeons can be confident in choosing either technique if rigorous patient selection, sound surgical technique, and proper hand therapy are employed. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Minimally invasive surgical approach to model hypertrophic scarring in the rabbit ear.

BACKGROUND: Current strategies for hypertrophic scar prevention and treatment are limited. OBJECTIVE: To facilitate these efforts, a minimally invasive hypertrophic scar model was created in a rabbit ear for the first time based on previous methods used to induce ischemia. METHODS: Six New Zealand white rabbits (12 ears total) were studied. First, ischemia was achieved by ligating the cranial artery, cranial vein and central artery, while preserving the caudal artery, caudal vein and central vein, respectively. The relative level of ischemia induced at time of surgery, both baseline and maximum perfusion, was assessed with a fluorescent light-assisted angiography and demonstrated lower rates of perfusion in the ischemic ears. Following vascular injury, a 2-cm full thickness linear wound was created on the ventral ear and closed with 4 - 0 Nylon sutures under high tension. For each rabbit, one ear received a combination of ischemia and wounding with suture tension (n = 6), while the other ear was non-ischemic with wounding and suture tension alone (n = 6). RESULTS: Four weeks post-operatively, ischemic ears developed scar hypertrophy (histological scar thickness: 1.1 ± 0.2 mm versus 0.5 ± 0.1 mm, p < 0.05). CONCLUSION: Herein, we describe a novel, prototypical minimally invasive rabbit ear model of hypertrophic scar formation that can allow investigation of new drugs for scar prevention.

Vanillylacetone attenuates cadmium chloride-induced hippocampal damage and memory loss through up-regulation of nuclear factor erythroid 2-related factor 2 gene and protein expression.

JOURNAL/nrgr/04.03/01300535-202412000-00030/figure1/v/2024-04-08T165401Z/r/image-tiff Memory loss and dementia are major public health concerns with a substantial economic burden. Oxidative stress has been shown to play a crucial role in the pathophysiology of hippocampal damage-induced memory impairment. To investigate whether the antioxidant and anti-inflammatory compound vanillylacetone (zingerone) can protect against hippocampal damage and memory loss induced by cadmium chloride (CdCl2) administration in rats, we explored the potential involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which is known to modulate oxidative stress and inflammation. Sixty healthy male Wistar rats were divided into five groups: vehicle-treated (control), vanillylacetone, CdCl2, vanillylacetone + CdCl2, vanillylacetone + CdCl2 + brusatol (a selective pharmacological Nrf2 inhibitor) groups. Vanillylacetone effectively attenuated CdCl2-induced damage in the dental gyrus of the hippocampus and improved the memory function assessed by the Morris Water Maze test. Additionally, vanillylacetone markedly decreased the hippocampal tissue levels of inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, intracellular cell adhesive molecules) and apoptosis biomarkers (Bax and cleaved caspase-3). The control and CdCl2-treated groups treated with vanillylacetone showed reduced generation of reactive oxygen species, decreased malondialdehyde levels, and increased superoxide dismutase and glutathione activities, along with significant elevation of nuclear Nrf2 mRNA and protein expression in hippocampal tissue. All the protective effects of vanillylacetone were substantially blocked by the co-administration of brusatol (a selective Nrf2 inhibitor). Vanillylacetone mitigated hippocampal damage and memory loss induced by CdCl2, at least in part, by activating the nuclear transcription factor Nrf2. Additionally, vanillylacetone exerted its potent antioxidant and anti-inflammatory actions.

Anti-viral Effects of Pavetta indica Methanolic Extract and Acyclovir on Behavioral and Biochemical Parameters in Streptozotocin-induced Alzheimer's Disease in Rats.

BACKGROUND: Alzheimer's disease is a neurological dysfunction of the brain caused by neurodegeneration and oxidative stress. Some viruses, such as herpes viruses, HSV-1, and HSV-2, are causative agents of Alzheimer's disease and result in ß-amyloid peptide and tau protein accumulation in the brain. Some antiviral drugs, such as valacyclovir, acyclovir, and foscarnet, reduce amyloid-beta and P-tau. Pavetta indica leaves are also reported for their antiviral properties. The current study aimed to find out the significance of using Pavetta indica methanolic extract and acyclovir against Alzheimer's disease induced by streptozotocin. METHODS: Wistar rats received acyclovir and Pavetta indica methanolic extract orally at different dose ranges (50, 150, 450 mg/kg) and (125, 250, 500 mg/kg), respectively. The standard therapy, Rivastigmine (2 mg/kg), was given orally. RESULTS: Intracerebroventricular-streptozotocin produced significant alternations in behavioral assessments, including locomotor activity test, Morris water maze test, and elevated plus maze test. Moreover, intracerebroventricular-streptozotocin ameliorated the antioxidant defense activity by decreasing levels of catalase, superoxide dismutase, and reduced glutathione while enhancing the oxidative stress markers, including malondialdehyde, and total nitrite levels. Finally, the main findings showed that intracerebroventricular-streptozotocin significantly increased the inflammatory marker, tumor necrosis factor-α, and disturbed neurotransmitter mediators, including levels of acetylcholinesterase, glutamate, and γ-amino butyric acid. CONCLUSION: In a dose-dependent manner, acyclovir and Pavetta indica methanolic extract treatments abrogated the streptozotocin-induced behavioral and neurological abnormalities in rats. The potential therapeutic effects of PIME and acyclovir administration in intracerebroventricular-streptozotocin-treated rats may be attributed to its potential antiviral, antioxidant, and anti-inflammatory effects. The current study suggests that Pavetta indica methanolic extract and acyclovir are promising therapeutic targets against Alzheimer's disease.

P4HA2 involved in SLUG-associated EMT predicts poor prognosis of patients with KRAS-positive colorectal cancer.

This study aimed to examine the immunohistochemical expression of epithelial-mesenchymal transition biomarkers: P4HA2 and SLUG in colorectal carcinoma (CRC) specimens, then to assess their relation to clinicopathological features including KRAS mutations and patients' survival, and finally to study the correlation between them in CRC. The result of this study showed that SLUG and P4HA2 were significantly higher in association with adverse prognostic factors: presence of lympho-vascular invasion, perineural invasion, higher tumor budding, tumor stage, presence of lymph node metastasis, and presence of distant metastasis. CRC specimens with KRAS mutation were associated with significant higher SLUG and P4HA2 expression. High expression of both SLUG and P4HA2 was significantly unfavorable prognostic indicator as regards overall survival (OS) and disease-free survival (DFS). In KRAS mutated cases, high P4HA2 expression was the only significant poor prognostic indicator as regarding DFS. In conclusions, our data highlight that both SLUG and P4HA2 expression may serve as potentially important poor prognostic biomarkers in CRC and targeting these molecules may be providing a novel therapeutic strategy. In KRAS mutation group, high P4HA2 expression is the only independent prognostic factor for tumor recurrence, so it can be suggested to be a novel target for therapy.

Free Vascularized Proximal Fibular Epiphyseal Transfer For Hip Reconstruction Following Septic Necrosis In Children.

BACKGROUND: Septic necrosis of the femoral head and neck in children represents a challenging problem. Several reconstructive techniques have been described but with disappointing long-term results. Vascularized epiphyseal transfer utilizing the proximal fibula have been successfully used for reconstruction of the proximal humerus and distal radius and only scarcely used for hip reconstruction. This cohort represents the largest reported series of epiphyseal transfer for hip reconstruction following septic necrosis in children. METHODS: A total of 18 patients with an average age at surgery of 5.4 years were included. The average follow-up was 3.6 years (range 2.3 to 6.8 y). RESULTS: Transient postoperative foot drop was observed in 4 patients. Radiographic resorption of the transferred fibula occurred in 2 cases. Longitudinal growth averaged 7.3 mm/year, and the physis width increased by an average of 2.7 mm/year. The rate of longitudinal growth was fastest after the age of 10 years (18.5 mm/y), which coincides with the pubertal growth spurt. All successful transfers had an open growth plate on final follow-up radiographs. Ten patients had limb length discrepancy of an average 2.8 cm (range 1 to 8 cm). Thirteen patients had satisfactory functional according to the criteria of Hunka et al. Three patients had unsatisfactory results; one had painful nonunion at the fibula-femur junction, and the other two had limited flexion range of 45 degrees. The average postoperative neck-shaft angle was 96.4 degrees which decreased by an average of 8 degrees at the final follow-up. Three patients underwent a valgus subtrochanteric osteotomy to correct a severe varus deformity. The final neck-shaft angle correlated significantly with the functional results where it averaged 96 degrees in the satisfactory group and 57 degrees in the unsatisfactory group. CONCLUSION: Vascularized epiphyseal transfer presents a promising treatment for children with septic necrosis of the femoral head and neck in whom other methods have failed to provide satisfactory long-term results. We recommend the procedure be done before the age of 5 years for optimum results. LEVEL OF EVIDENCE: Level-IV.

Improvement of Na+-K+ ATPase Activity and Gene Expression Associated with Glomerular Ultrastructural Protection in Diabetic Nephropathy by Acacia senegal: Role of Oxidative Stress Disturbances / Mejora de la actividad Na+-K+ ATPasa y la Expresión Génica Asociada con la Protección Ultraestructural Glomerular en la Nefropatía Diabética por Acacia senegal: Papel de las Alteraciones del Estrés Oxidativo

SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.

Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.

The Outcome of Congenital Cardiac Surgery in Patients with Down Syndrome: Single-Center Experience.

OBJECTIVES: This study aimed to describe the outcomes of Down syndrome patients who underwent cardiac surgery for congenital heart defects and to develop risk prediction models for in-hospital mortality, recurrent hospital admission, and the need for catheter intervention among a cohort of patients. METHODS: This single-centre retrospective cohort study included consecutive Down syndrome patients who underwent cardiac surgery for congenital heart defects between January 2018 and December 2021. We reviewed the electronic medical records. Two hundred patients fulfilled the eligibility criteria with complete data reporting. The patients' perioperative data and outcomes were recorded. RESULTS: Females constituted 56.5%. Most (78.5%) patients showed accepted recovery. The incidence of all-cause in-hospital mortality was 3.0%. The rates of the need for a second operation, heart failure management, and permanent pacemaker insertion were 3.0%, 2.0%, and 2.5%, respectively. Only 8 (4.0%) patients stayed in the hospital for a long duration after chylothorax or tracheostomy (if intubated more than 2 weeks). The model had an accuracy of 99% and included the intraoperative transesophageal echocardiography (TEE) abnormalities (residual heart lesions) (adjusted odds ratio [AOR]: 26.541, p = 0.033), the duration of mechanical ventilation following the operation (AOR: 1.152, p = 0.009), and the occurrence of postoperative heart block (AOR: 76.447, p = 0.005). CONCLUSION: Surgical treatment of congenital heart defects in Down syndrome patients had good outcomes with accepted recovery (without intra-hospital or during follow-up mortality or morbidity) of 78.5% and a 3% incidence of in-hospital mortality. Though, the occurrence of chylothorax was considerably high, and resulted in a long hospital stay (more than 10 days). Repair of tetralogy of Fallot and coarctation of the aorta were associated with an increased likelihood of catheter intervention following the operation.

Arthroscopic Management of Juxta-articular Proximal Humeral Chondroblastoma: The Bazooka Technique.

Chondroblastoma is a rare benign cartilaginous lesion located mostly in the epiphyses of the long bones. The most common locations are the proximal tibia or femur, distal femur, and proximal humerus. Open curettage and bone grafting constitute the mainstay treatment for this condition. Few reports have documented the use of arthroscopy in tumor surgery owing to the problem of inadequate removal and the difficulty of bone graft delivery to the tumor cavity. The bazooka technique should solve these 2 main problems. In this article, arthroscopic curettage and grafting are described for the treatment of juxta-articular proximal humeral chondroblastoma to lessen postoperative pain and thus enable early mobilization and a quicker rehabilitation in skeletally immature patients.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: An Emerging Diagnostic and Therapeutic Biomolecules for Neurodegenerative Disabilities.

Mesenchymal stem cells (MSCs) are a type of versatile adult stem cells present in various organs. These cells give rise to extracellular vesicles (EVs) containing a diverse array of biologically active elements, making them a promising approach for therapeutics and diagnostics. This article examines the potential therapeutic applications of MSC-derived EVs in addressing neurodegenerative disorders such as Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). Furthermore, the present state-of-the-art for MSC-EV-based therapy in AD, HD, PD, ALS, and MS is discussed. Significant progress has been made in understanding the etiology and potential treatments for a range of neurodegenerative diseases (NDs) over the last few decades. The contents of EVs are carried across cells for intercellular contact, which often results in the control of the recipient cell's homeostasis. Since EVs represent the therapeutically beneficial cargo of parent cells and are devoid of many ethical problems connected with cell-based treatments, they offer a viable cell-free therapy alternative for tissue regeneration and repair. Developing innovative EV-dependent medicines has proven difficult due to the lack of standardized procedures in EV extraction processes as well as their pharmacological characteristics and mechanisms of action. However, recent biotechnology and engineering research has greatly enhanced the content and applicability of MSC-EVs.

Treatment of Concomitant Congenital Pseudarthrosis of the Fibula With Propeller Periosteal Flap.

INTRODUCTION: Congenital pseudarthrosis of the fibula is not an uncommon condition to accompany congenital pseudarthrosis of the tibia. Persistence of the fibular pseudarthrosis has been linked to inferior outcomes including tibial union and alignment, refractures, and ankle alignment. In this report, we present the results of a pedicled periosteal propeller flap technique for the treatment of fibular pseudarthrosis. METHODS: Ten children with an average age at surgery of 5.3 years who had congenital pseudarthrosis of both tibia and fibula were studied. The tibia was treated with free vascularized fibular grafting, and the ipsilateral fibula was treated with a technique after resection of the pseudarthrosis. A periosteal flap from the proximal healthy part of the fibula is harvested off the bone, rotated 180° based on a branch from the peroneal vessels to cover the fibular defect and fashioned in the form of a tube filled with bone fragments. RESULTS: The periosteal flap size ranged from 5 to 7 cm. Follow-up averaged 37.2 months. The tibia was united in all cases; in 2 of them, refractures occurred and healed with conservative management. The fibula was united in 8 cases. At final follow-up, 5 cases showed residual tibial deformity, and 5 showed residual ankle deformity. Average leg-length discrepancy was 1.4 cm (0-3 cm). CONCLUSION: The pedicled periosteal propeller flap presents a useful new technique for managing concomitant congenital fibular pseudarthrosis.

Pregnenolone Inhibits Doxorubicin-Induced Cardiac Oxidative Stress, Inflammation, and Apoptosis-Role of Matrix Metalloproteinase 2 and NADPH Oxidase 1.

The clinical usefulness of doxorubicin (DOX) is limited by its serious adverse effects, such as cardiotoxicity. Pregnenolone demonstrated both anti-inflammatory and antioxidant activity in animal models. The current study aimed to investigate the cardioprotective potential of pregnenolone against DOX-induced cardiotoxicity. After acclimatization, male Wistar rats were randomly grouped into four groups: control (vehicle-treated), pregnenolone (35 mg/kg/d, p.o.), DOX (15 mg/kg, i.p, once), and pregnenolone + DOX. All treatments continued for seven consecutive days except DOX, which was administered once on day 5. The heart and serum samples were harvested one day after the last treatment for further assays. Pregnenolone ameliorated the DOX-induced increase in markers of cardiotoxicity, namely, histopathological changes and elevated serum levels of creatine kinase-MB and lactate dehydrogenase. Moreover, pregnenolone prevented DOX-induced oxidative changes (significantly lowered cardiac malondialdehyde, total nitrite/nitrate, and NADPH oxidase 1, and elevated reduced glutathione), tissue remodeling (significantly decreased matrix metalloproteinase 2), inflammation (significantly decreased tumor necrosis factor-α and interleukin 6), and proapoptotic changes (significantly lowered cleaved caspase-3). In conclusion, these findings show the cardioprotective effects of pregnenolone in DOX-treated rats. The cardioprotection achieved by pregnenolone treatment can be attributed to its antioxidant, anti-inflammatory, and antiapoptotic actions.

Congenital Pseudarthrosis of the Tibia: Long-term Outcome of Treatment With Intramedullary Vascularized Fibular Graft Combined With Ilizarov Distraction.

BACKGROUND: Late presenting cases of congenital pseudarthrosis of the tibia, are further complicated with severe shortening. Limb length discrepancy (LLD) cannot be corrected by vascularized fibular grafting and the use of Ilizarov distraction is associated with a high rate of complications. The aim of this study was to report the long-term follow-up of a combined technique previously published under the name "telescoping vascularized fibular graft". MATERIALS AND METHODS: Eleven patients operated at an average age of 10.2±3.2 years were reviewed. All cases were Crawford type IV affected by neurofibromatosis 1. Nine patients had an average of 4.3 previous operations. Preoperative LLD averaged 7.9±2.5 cm. RESULTS: Follow-up averaged 10±5.4 years. Seven cases (63.6%) reached skeletal maturity before final follow-up. Primary union was achieved in all cases after an average of 7.2±1.3 months. Full weightbearing was possible after an average of 10.6±2.2 months. Recurrent stress fractures occurred in 9 cases (81.8%) and healed with casting in 6 cases and required internal fixation in 3 cases. Eight cases (72.8%) developed tibial shaft deformities, mainly procurvatum that required corrective osteotomy in 2 cases. Final LLD averaged 2.7±1.3 cm. Complete tibialization of the graft was achieved after an average of 17.0 ± 3.6 months. Valgus deformity of the ipsilateral ankle averaged 12.4 degrees±7.5. CONCLUSION: The presented technique avoids osteotomy of the diseased bone and allows simultaneous treatment of the pseudarthrosis and correction of shortening. Compared with conventional bone transport, it requires shorter time of frame application and therefore better patient tolerability because there is no waiting for consolidation of the regenerate. The dis-impaction of the doweled fibula occurs proximally, allowing the less active site located at the distal aspect of the pseudarthrosis to heal without displacement. A shortcoming of the presented technique is the more propensity for axial deviation and refractures that seldom require surgery. LEVEL OF EVIDENCE: Level-IV.

Fixation of Mallet Fractures Using a Modified Hook Plate Technique: A Prospective Case Series of 17 Patients / Fixação de fraturas em martelo com técnica de placa de gancho modificada: Uma série de casos prospectivos de 17 pacientes

Abstract Objective Various modalities have been suggested to manage mallet fractures; however, inappropriate treatment can lead to extension lag, a swan neck deformity, or arthritis of the distal interphalangeal joint (DIPJ). The current study aimed to evaluate the results (functional, radiological, and complications) of open reduction and internal fixation (ORIF) of mallet fractures using low-cost hook plates fabricated from low-profile titanium mini plates. Methods A prospective case series of 17 consecutive patients (average age of 32.3 years) with mallet fractures (six were Wehbe Type IB and 11 were Wehbe Type MB). Eleven (64.7%) were males. The affected hand was dominant in all patients, and the affected digit was the index in 6 (35.3%), the ring in 5 (29.4%), the small in 3 (17.65%), and the middle in 3 (17.65%) patients. The same fellowship-trained hand surgeon performed all surgeries. Results The average operative time was 37.65 minutes. After an average follow-up of 10.94 months (range 6-27), the average DIPJ motion was 50º º (range 20º-70º), the extensor lag was noted in 4 (23.5%) patients, and complications were reported in 6 (35.29%) patients. According to Crawford criteria, 6 (35.3%) patients achieved excellent results, 7 (41.2%) achieved good results, and 4 (23.5%) achieved fair results. Conclusion The modified hook plate technique for fixation of mallet fractures is a beneficiai, economical, yet demanding technique that adequately provides stable fixation to allow early DIPJ motion with acceptable functional outcomes.

Resumo Objetivo Diversas modalidades têm sido sugeridas para o tratamento de fraturas em martelo; no entanto, o tratamento inadequado pode causar retardo de extensão, deformidade em pescoço de cisne ou artrite da articulação interfalangiana distal (AIFD). Este estudo teve como objetivo avaliar os desfechos (funcionais, radiológicos e complicações) da redução aberta e fixação interna (RAFI) das fraturas em martelo com placas de gancho de baixo custo fabricadas com mini placas de titânio de baixo perfil. Métodos Série de casos prospectivos de 17 pacientes consecutivos (idade média de 32,3 anos) com fraturas em martelo (seis do tipo IB e 11 do tipo IIB de Wehbe). Onze (64,7%) pacientes eram do sexo masculino. A mão acometida era a dominante em todos os pacientes, com acometimento do dedo indicador em seis (35,3%), anelar em cinco (29,4%), mínimo em três (17,65%) e médio em três (17,65%) pacientes. O mesmo cirurgião de mão experiente realizou todas as cirurgias. Resultados O tempo operatório médio foi de 37,65 minutos. Após um acompanhamento médio de 10,94 meses (intervalo de 6 a 27), observou-se movimento médio da AIFD de 50º (intervalo de 20º a 70º), retardo de extensão em quatro (23,5%) pacientes e complicações em seis (35,29%) pacientes. De acordo com os critérios de Crawford, os desfechos foram excelentes em seis (35,3%), bons em sete (41,2%) e regulares em quatro (23,5%) pacientes. Conclusão A técnica da placa de gancho modificada para fixação de fraturas em martelo é benéfica e econômica, mas exigente; permite fixação estável e adequada para permitir a movimentação precoce da AIFD com desfechos funcionais aceitáveis.

QTRAP LC/MS/MS of Garlic Nanoparticles and Improving Sunflower Oil Stabilization during Accelerated Shelf Life Storage.

The purpose of this research was to assess and utilize the bioactive compounds of garlic nanoparticles (Ga-NPs) as a natural antioxidant in sunflower oil (SFO) stored at 65 ± 1 °C for 24 days. The garlic nanoparticles (Ga-NPs) from the Balady cultivar were prepared, characterized, and added to SFO at three concentrations: 200, 600, and 1000 ppm (w/v), and they were compared with 600 ppm garlic lyophilized powder extract (Ga-LPE), 200 ppm BHT, 200 ppm α-tocopherol, and SFO without Ga-NPs (control). The QTRAP LC/MS/MS profile of Ga-NPs revealed the presence of four organosulfur compounds. Ga-NPs exhibited the highest capacity for phenolic, flavonoid, and antioxidant compounds. In Ga-NP SFO samples, the values of peroxide, p-anisidine, totox, conjugated dienes, and conjugated trienes were significantly lower than the control. The antioxidant indices of SFO samples containing Ga-NPs were higher than the control. The Ga-NPs enhanced the sensory acceptability of SFO treatments up to day 24 of storage. The shelf life of SFO treated with Ga-NPs was substantially increased (presuming a Q10 amount). The results show that Ga-NPs are a powerful antioxidant that improves SFO stability and extends the shelf life (~384 days at 25 °C).

Tocotrienol in the Treatment of Topical Wounds: Recent Updates.

Healing wounds is an important attempt to keep the internal higher organs safe. Complications in topical wound healing may lead to the formation of scars, which can affect the patient's quality of life. Although several approaches are ongoing in parallel in the exploration of natural compounds via advanced delivery, in this article, an attempt has been made to highlight tocotrienol. Tocotrienol is a natural form of vitamin E and has shown its potential in certain pharmacological activities better than tocopherol. Its antioxidant, anti-inflammatory, cell signal-mediating effects, angiogenic properties, management of scar, and promotion of wound environment with essential factors have shown potential in the management of topical wound healing. Therefore, this review has aimed to focus on recent advances in topical wound healing through the application of tocotrienols. Challenges in delivering tocotrienols to the topical wound due to its large molecular weight and higher logP have also been explored using nanotechnological-based carriers, which has made tocotrienol a potential tool to facilitate the closure of wounds. Exploration of tocotrienol has also been made in human volunteers for biopsy wounds; however, the results are yet to be reported. Overall, based on the current findings in the literature, it could be inferred that tocotrienol would be a viable alternative to the existing wound dressing components for the management of topical wounds.

Carnosine Potentiates Doxorubicin-Induced Cytotoxicity in Resistant NCI/ADR-RES Cells by Inhibiting P-Glycoprotein-In Silico and In Vitro Evidence.

The activity of the P-glycoprotein (P-gp) transporter encoded by the ABCB1 gene confers resistance to anticancer drugs and contributes to cancer-related mortality and morbidity. Recent studies revealed the cytotoxic effects of the endogenous dipeptide carnosine. The current study aimed to investigate the role of carnosine as a potential inhibitor of P-gp activity. We used molecular docking and molecular dynamic simulations to study the possible binding and stability of carnosine-P-gp interactions compared with verapamil. In vitro assays using doxorubicin-resistant NCI/ADR-RES cells were established to test the effects of carnosine (10-300 µM) on P-gp activity by the rhodamine-123 efflux assay and its effect on cell viability and doxorubicin-induced cytotoxicity. Verapamil (10 µM) was used as a positive control. The results showed that carnosine binding depends mainly on hydrogen bonding with GLU875, GLN946, and ALA871, with a higher average Hbond than verapamil. Carnosine showed significant but weaker than verapamil-induced rhodamine-123 accumulation. Carnosine and verapamil similarly inhibited cell viability. However, verapamil showed a more significant potentiating effect on doxorubicin-induced cytotoxicity than a weaker effect of carnosine at 300 µM. These results suggest that carnosine inhibits P-gp activity and potentiates doxorubicin-induced cytotoxicity at higher concentrations. Carnosine might be a helpful lead compound in the fight against multidrug-resistant cancers.

Paeonol Protects against Methotrexate Hepatotoxicity by Repressing Oxidative Stress, Inflammation, and Apoptosis-The Role of Drug Efflux Transporters.

Methotrexate (MTX) is an effective chemotherapeutic agent against a wide range of tumors and autoimmune diseases; however, hepatotoxicity limits its clinical use. Oxidative stress and inflammation have been implicated in the pathogenesis of MTX-induced hepatotoxicity. Paeonol is a natural phenolic compound reported for its antioxidant and anti-inflammatory properties. The current study aimed to investigate the protective effect of paeonol against MTX-induced hepatotoxicity in rats and various mechanisms that underlie this postulated effect. Paeonol was administered orally in a dose of 100 mg/kg, alone or along with MTX, for 10 days. Hepatotoxicity was induced via a single intraperitoneal dose of MTX (20 mg/kg) on day 5 of the experiment. Concomitant administration of paeonol with MTX significantly ameliorated distorted hepatic function and histological structure, restored hepatic oxidative stress parameters (MDA, NO, and SOD), and combated inflammatory response (iNOS and TNF-α). Additionally, paeonol enhanced cell proliferation and survival, evidenced by upregulating the proliferating cell nuclear antigen (PCNA) and suppressing apoptosis and the disposition of collagen fibers in rat livers treated with MTX. Importantly, paeonol upregulated the drug efflux transporters, namely P-glycoprotein (P-gp) and the multidrug resistance-associated protein 2 (Mrp-2) in MTX-treated rats. In conclusion, paeonol offered a potent protective effect against MTX-induced hepatotoxicity through suppressing oxidative stress, inflammation, fibrosis, and apoptosis pathways, along with P-gp and Mrp-2 upregulation.

Ameliorative Effect of Dabigatran on CFA-Induced Rheumatoid Arthritis via Modulating Kallikrein-Kinin System in Rats.

Rheumatoid arthritis is an autoimmune disease that affects joints, leading to swelling, inflammation, and dysfunction in the joints. Recently, research efforts have been focused on finding novel curative approaches for rheumatoid arthritis, as current therapies are associated with adverse effects. Here, we examined the effectiveness of dabigatran, the antithrombotic agent, in treating complete Freund's adjuvant (CFA)-induced arthritis in rats. Subcutaneous injection of a single 0.3 mL dosage of CFA into the rat's hind leg planter surface resulted in articular surface deformities, reduced cartilage thickness, loss of intercellular matrix, and inflammatory cell infiltration. There were also increased levels of the Anti-cyclic citrullinated peptide antibody (ACPA), oxidative stress, and tissue Receptor activator of nuclear factor-kappa B ligand (RANKL). Proteins of the kallikrein-kinin system (KKS) were also elevated. The inhibitory effects of dabigatran on thrombin led to a subsequent inhibition of KKS and reduced Toll-like receptor 4 (TLR4) expression. These effects also decreased RANKL levels and showed anti-inflammatory and antioxidant effects. Therefore, dabigatran could be a novel therapeutic strategy for arthritis.