Estimated impact of guidelines-based initiation of dual antihypertensive therapy on long-term cardiovascular outcomes in 1.1 million individuals.

AIMS: Guidelines recommend initiation of dual combination antihypertensive therapy, preferably single-pill combination (SPC), in most patients with hypertension. Evidence on narrowing gaps in clinical practice relative to guidelines is limited. METHODS AND RESULTS: Monte Carlo simulation was applied to 1.1 million patients qualifying for dual combination therapy from a previously conducted retrospective analysis of clinical practice, hospital statistics, and national statistics in the UK. We provide 10-year Kaplan-Meier event rates for the primary endpoint representing a composite of nonfatal myocardial infarction, nonfatal stroke (ischemic or hemorrhagic), nonfatal heart failure hospitalization or cardiovascular death. Cox model results from a previously conducted study were utilized to estimate baseline risk, together with evidence on risk reduction from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) meta-analysis and published evidence on BP-lowering efficacy of antihypertensive therapies. In the overall population, estimated 10-year event rates for the primary endpoint in patients with 100% persistence in monotherapy were 17.0% for irbesartan (I) and 17.6% for ramipril (R). These rates were only modestly better than that observed in clinical practice (17.8%). In patients with 100% persistence in dual therapy, estimated event rates were 13.6% for combinations of Irbesartan + Amlodipine (ARR = 8.7% compared to untreated) and 14.3% for Ramipril + Amlodipine (ARR = 8.0% compared to untreated). The absolute risk of the primary endpoint was reduced by 15.9% in patients with ASCVD and 6.6% in those without ASCVD. Similarly, the absolute risk was reduced by 11.7% in diabetics and 7.8% in those without diabetes. CONCLUSION: This study represents the first to investigate guidelines-based treatment in hypertensive patients and demonstrates the opportunity for considerable risk reduction by ensuring recommended dual therapy in clinical practice, particularly in the form of SPC with high persistence, relative to no treatment or monotherapy.

Pharmacological activation of mesenchymal stem cells increases gene expression pattern of cell adhesion molecules and fusion with neonatal cardiomyocytes.

Cellular therapy is considered a better option for the treatment of degenerative disorders. Different cell types are being used for tissue regeneration. Despite extensive research in this field, several issues remain to be addressed concerning cell transplantation. One of these issues is the survival and homing of administered cells in the injured tissue, which depends on the ability of these cells to adhere. To enhance cell adherence and survival, Rap1 GTPase was activated in mesenchymal stem cells (MSCs) as well as in cardiomyocytes (CMs) by using 8-pCPT-2'-O-Me-cAMP, and the effect on gene expression dynamics was determined through quantitative reverse transcriptase-polymerase chain reaction analysis. Pharmacological activation of MSCs and CMs resulted in the upregulation of connexin-43 and cell adhesion genes, which increased the cell adhesion ability of MSCs and CMs, and increased the fusion of MSCs with neonatal CMs. Treating stem cells with a pharmacological agent that activates Rap1a before transplantation can enhance their fusion with CMs and increase cellular regeneration.

Alpha terpineol preconditioning enhances regenerative potential of mesenchymal stem cells in full thickness acid burn wounds.

Regeneration of full thickness burn wounds is a significant clinical challenge. Direct stem cell transplantation at the wound site has a promising effect on wound regeneration. However, stem cell survival within the harsh wound environment is critically compromised. In this regard, preconditioning of stem cells with cytoprotective compounds can improve the efficiency of transplanted cells. This study evaluated the possible effect of alpha terpineol (αT) preconditioned mesenchymal stem cells (αT-MSCs) in full thickness acid burn wound. An optimized concentration of 10 µM αT was used for MSC preconditioning, followed by scratch assay analysis. A novel rat model of full thickness acid burn wound was developed and characterized via macroscopic and histological examinations. Treatment (normal and αT-MSCs) was given after 48 h of burn wound induction, and the healing pattern was examined till day 40. Skin tissues were harvested at the early (day 10) and late (day 40) wound healing phases and examined by histological grading, neovascularization, and gene expression profiling of healing mediators. In scratch assay, αT-MSCs exhibited enhanced cell migration and wound closure (scratch gap) compared to normal MSCs. In vivo findings revealed enhanced regeneration in the wound treated with αT-MSCs compared to normal MSCs and untreated control. Histology revealed enhanced collagen deposition with regenerated skin layers in normal MSC- and αT-MSC treated groups compared to the untreated control. These findings were correlated with enhanced expression of α-SMA as shown by immunohistochemistry. Additionally, αT-MSC group showed reduced inflammation and oxidative stress, and enhanced regeneration, as witnessed by a decrease in IL-1ß, IL-6, TNF-α, and Bax and an increase in BCL-2, PRDX-4, GPX-7, SOD-1, VEGF, EGF, FGF, MMP-9, PDGF, and TGF-ß gene expression levels at early and late phases, respectively. Overall findings demonstrated that αT exerts its therapeutic effect by mitigating excessive inflammation and oxidative stress while concurrently enhancing neovascularization. Thus, this study offers new perspectives on managing full thickness acid burn wounds in future clinical settings.

Management of Massive Flank Hernia After Lateral Lumbar Fusion: Preoperative Botulinum Toxin Injections and Open Repair - A Case Report.

BACKGROUND Incisional flank hernias represent a complication after lateral lumbar spine surgery. Given the increasing rate of lateral lumbar interbody fusions, the rate of incisional flank hernias will increase. Since there are no reports of open massive flank hernia repair utilizing preoperative botulinum injections, we sought to publish this technique to provide surgeons with an innovative method for preoperatively treating patients with massive flank hernias. CASE REPORT A 75-year-old man with a history of coronary artery disease, chronic kidney disease, and abdominal hernia repair presented for evaluation of left lateral abdominal and left lower back bulging for 5 months. The symptoms began after an L2-L4 lateral lumbar spinal fusion. Physical examination revealed a left posterior lateral flank bulge. Computed tomography (CT) showed a fat-containing left posterolateral abdominal hernia. The patient was scheduled for CT-guided lateral abdominal wall botulinum injections, followed by open flank hernia repair. He tolerated the surgery well, was admitted for pain control, and discharged on day 2. Repeat imaging with CT at 3 months showed no evidence of patient's prior hernia defect. CONCLUSIONS Open flank hernia repair, in conjunction with preoperative botulinum toxin injections, allows for optimal visualization and re-approximation of the myofascial components of flank hernia defects. Failure to achieve adequate myofascial and skin closure, along with mesh reinforcement, in open flank hernia repair can result in various surgical site complications, including incisional flank hernia recurrence. We recommend further investigation on the benefits of botulinum injections as an adjunct in management of massive flank hernias.

Causal Effects of Inflammatory Bowel Diseases on the Risk of Kidney Stone Disease.

BACKGROUND: Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, have been increasingly associated with kidney stone disease, posing significant health challenges globally. OBJECTIVE: This research sought to determine the causal relationship between kidney stone disease risk and inflammatory bowel disorders. METHODOLOGY: This retrospective cohort study included patients with IBDs, such as ulcerative colitis or Crohn's disease, who were diagnosed at least 18 years of age. Information was gathered with an emphasis on patients having comprehensive medical histories and confirmed cases of kidney stone disease from January to December 2022. Medical records were retrospectively evaluated by trained staff to extract treatment information and clinical, radiological, and demographic data. To evaluate relationships, statistical analysis was carried out in SPSS software version 23 using Chi-square tests and descriptive statistics. RESULTS: The study included 320 patients diagnosed with IBDs, among which 198 (61.87%) had Crohn's disease, and 122 (38.13%) were diagnosed with ulcerative colitis. The cohort consisted of 140 females (43.75%) and 180 men (56.25%), with a mean age of 45.5 years. Regarding smoking, 113 people (35.31%) reported being smokers, whereas 207 people (64.69%) did not smoke. Additionally, 18 (5.62%) of the population had an underweight BMI, 136 (42.50%) had a normal BMI, 119 (37.19%) had an overweight BMI, and 47 (14.69%) had an obese BMI. Of the patients, 86 (26.88%) had a prior history of kidney stone disease, while 194 (60.62%) did not. Aminosalicylates were the most often used therapy modality for IBD in 189 (58.97%) of cases, followed by corticosteroids in 117 (36.56%) and immunomodulators in 93 (28.94%). Radiological examinations showed that renal calculi were present in 60 (18.75%) of patients, and kidney stones occurred in 40 (12.50%) of patients throughout the research period. The smoking status (p=0.006) and prior history of kidney stones (p<0.001) were the corresponding p-values for the significant results. CONCLUSION: The study highlights an increased risk of kidney stone disease in IBD patients, particularly among smokers and those with a recurrent history of kidney stones. Of the 320 patients, 198 (61.87%) had Crohn's disease and 122 (38.13%) had ulcerative colitis, with a significant relationship found between kidney stones and both smoking (113 patients, 35.31%, p=0.006) and a prior history of kidney stones (86 patients, 26.88%, p<0.001). The findings emphasize the need for targeted preventive measures and close monitoring of these high-risk groups.

Implications of Microbiota and Immune System in Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent type of liver disease worldwide. The exact pathophysiology behind MASLD remains unclear; however, it is thought that a combination of factors or "hits" act as precipitants for disease onset and progression. Abundant evidence supports the roles of diet, genes, metabolic dysregulation, and the intestinal microbiome in influencing the accumulation of lipids in hepatocytes and subsequent progression to inflammation and fibrosis. Currently, there is no cure for MASLD, but lifestyle changes have been the prevailing cornerstones of management. Research is now focusing on the intestinal microbiome as a potential therapeutic target for MASLD, with the spotlight shifting to probiotics, antibiotics, and fecal microbiota transplantation. In this review, we provide an overview of how intestinal microbiota interact with the immune system to contribute to the pathogenesis of MASLD and metabolic dysfunction-associated steatohepatitis (MASH). We also summarize key microbial taxa implicated in the disease and discuss evidence supporting microbial-targeted therapies in its management.

Impact of energy imports, renewable electricity production, alternative, and nuclear energy sources on natural gas resource rents.

The world faces several problems related to natural gas resource rents and energy production from renewable sources. One of the main problems is the influence of energy imports, manufacturing exports, and alternative energy sources on natural gas and electricity production from renewable sources. Energy imports, manufacturing exports, and alternative energy sources can impact natural gas and electricity production. This paper examines natural gas resource rents and electricity production from renewable sources nexus from 1971 to 2021, using energy imports, manufacturer's exports, and alternative energy sources in China. Electricity production from renewable sources and manufacturing exports are negatively associated with natural gas resource rents. Energy imports and alternative energy sources positively relate to natural gas resource rents in China. These results suggest that the energy sector in China is highly interconnected and that policies that seek to promote renewable energy sources and other alternatives can positively affect natural gas resource rents. China needs to develop an energy policy considering the policy implications of energy imports and natural gas resource rents. Such a policy should focus on increasing domestic production, reducing energy imports, and ensuring adequate revenue from natural gas resource rents. Additionally, regulations could be implemented that support the development of alternative energy sources, such as requiring utilities to purchase a certain percentage of their power from renewable sources.

Surgeons Experience Greater Physiologic Stress and Strain in the Direct Anterior Approach Than the Posterior Approach for Total Hip Arthroplasty.

BACKGROUND: The direct anterior approach (DAA) and posterior approach (PA) for total hip arthroplasty (THA) have advantages and disadvantages, but their physiologic burden to the surgeon has not been quantified. This study was conducted to determine whether differences exist in surgeon physiological stress and strain during DAA in comparison to PA. METHODS: We evaluated a prospective cohort of 144 consecutive cases (67 DAA and 77 PA). There were 5, high-volume, fellowship-trained arthroplasty surgeons who wore a smart-vest that recorded cardiorespiratory data while performing primary THA DAA or PA. Heart rate (beats/minute), stress index (correlates with sympathetic activations), respiratory rate (respirations/minute), minute ventilation (L/min), and energy expenditure (calories) were recorded, along with patient body mass index and operative time. Continuous data was compared using t-tests or Mann Whitney U tests, and categorical data was compared with Chi-square or Fischer's exact tests. RESULTS: There were no differences in patient characteristics. Compared to PA, performing THA via DAA had a significantly higher surgeon stress index (17.4 versus 12.4; P < .001), heart rate (101 versus 98.3; P = .007), minute ventilation (21.7 versus 18.7; P < .001), and energy expenditure per hour (349 versus 295; P < .001). However, DAA had a significantly shorter operative time (71.4 versus 82.1; P = .001). CONCLUSIONS: Surgeons experience significantly higher physiological stress and strain when performing DAA compared to PA for primary THA. This study provides objective data on energy expenditure that can be factored into choice of approach, case order, and scheduling preferences, and provides insight into the work done by the surgeon.

Expansion of human umbilical cord derived mesenchymal stem cells in regenerative medicine.

BACKGROUND: Stem cells are undifferentiated cells that possess the potential for self-renewal with the capacity to differentiate into multiple lineages. In humans, their limited numbers pose a challenge in fulfilling the necessary demands for the regeneration and repair of damaged tissues or organs. Studies suggested that mesenchymal stem cells (MSCs), necessary for repair and regeneration via transplantation, require doses ranging from 10 to 400 million cells. Furthermore, the limited expansion of MSCs restricts their therapeutic application. AIM: To optimize a novel protocol to achieve qualitative and quantitative expansion of MSCs to reach the targeted number of cells for cellular transplantation and minimize the limitations in stem cell therapy protocols. METHODS: Human umbilical cord (hUC) tissue derived MSCs were obtained and re-cultured. These cultured cells were subjected to the following evaluation procedures: Immunophenotyping, immunocytochemical staining, trilineage differentiation, population doubling time and number, gene expression markers for proliferation, cell cycle progression, senescence-associated ß-galactosidase assay, human telomerase reverse transcriptase (hTERT) expression, mycoplasma, cytomegalovirus and endotoxin detection. RESULTS: Analysis of pluripotent gene markers Oct4, Sox2, and Nanog in recultured hUC-MSC revealed no significant differences. The immunophenotypic markers CD90, CD73, CD105, CD44, vimentin, CD29, Stro-1, and Lin28 were positively expressed by these recultured expanded MSCs, and were found negative for CD34, CD11b, CD19, CD45, and HLA-DR. The recultured hUC-MSC population continued to expand through passage 15. Proliferative gene expression of Pax6, BMP2, and TGFb1 showed no significant variation between recultured hUC-MSC groups. Nevertheless, a significant increase (P < 0.001) in the mitotic phase of the cell cycle was observed in recultured hUC-MSCs. Cellular senescence markers (hTERT expression and ß-galactosidase activity) did not show any negative effect on recultured hUC-MSCs. Additionally, quality control assessments consistently confirmed the absence of mycoplasma, cytomegalovirus, and endotoxin contamination. CONCLUSION: This study proposes the development of a novel protocol for efficiently expanding stem cell population. This would address the growing demand for larger stem cell doses needed for cellular transplantation and will significantly improve the feasibility of stem cell based therapies.

Single dose human perinatal stem cells accelerate healing of cold-induced rat burn wound.

Temporal phases of wound healing and their corresponding healing factors are essential in wound regeneration. Mesenchymal stem cells (MSCs) accelerate wound healing via their paracrine secretions by enhancing cell migration, angiogenesis, and reducing inflammation. This study evaluated the local therapeutic effect of human umbilical cord MSCs (hUCMSCs) in the healing of cold-induced burn wounds. An in vitro wound (scratch) was developed in rat skin fibroblasts. The culture was maintained in the conditioned medium (CM) which was prepared by inducing an artificial wound in hUCMSCs in a separate experiment. Treated fibroblasts were analyzed for the gene expression profile of healing mediators involved in wound closure. Findings revealed enhanced cell migration and increased levels of healing mediators in the treated fibroblasts relative to the untreated group. Cold-induced burn wounds were developed in Wistar rats, followed by a single injection of hUCMSCs. Wound healing pattern was examined based on the healing phases: hemostasis/inflammation (Days 1, 3), cell proliferation (Day 7), and remodeling (Day 14). Findings exhibited enhanced wound closure in the treated wound. Gene expression, histological, and immunohistochemical analyses further confirmed enhanced wound regeneration after hUCMSC transplantation. Temporal gene expression profile revealed that the level of corresponding cytokines was substantially increased in the treated wound as compared with the control, indicating improvement in the processes of angiogenesis and remodeling, and a substantial reduction in inflammation. Histology revealed significant collagen formation along with regenerated skin layers and appendages, whereas immunohistochemistry exhibited increased neovascularization during remodeling. Leukocyte infiltration was also suppressed in the treated group. Overall findings demonstrate that a single dose of hUCMSCs enhances wound healing in vivo, and their secreted growth factors accelerate cell migration in vitro.

Comprehensive characterization of genomic features and clinical outcomes following targeted therapy and secondary cytoreductive surgery in OCCC: a single center experience.

OBJECTIVE: Ovarian clear cell carcinoma (OCCC) is associated with chemoresistance. Limited data exists regarding the efficacy of targeted therapies such as immune checkpoint inhibitors (ICI) and bevacizumab, and the role of secondary cytoreductive surgery (SCS). METHODS: We retrospectively analyzed genomic features and treatment outcomes of 172 OCCC patients treated at our institution from January 2000 to May 2022. Next-generation sequencing (NGS) was performed where sufficient archival tissue was available. RESULTS: 64.0% of patients were diagnosed at an early stage, and 36.0% at an advanced stage. Patients with advanced/relapsed OCCC who received platinum-based chemotherapy plus bevacizumab followed by maintenance bevacizumab had a median first-line progression-free survival (PFS) of 12.2 months, compared with 9.3 months for chemotherapy alone (hazard ratio=0.69; 95% confidence interval [CI]=0.33, 1.45). In 27 patients who received an ICI, the overall response rate was 18.5% and median duration of response was 7.4 months (95% CI=6.5, 8.3). In 17 carefully selected patients with fewer than 3 sites of relapse, median PFS was 35 months (95% CI=0, 73.5) and median overall survival was 96.8 months (95% CI=44.6, 149.0) after SCS. NGS on 58 tumors revealed common mutations in ARID1A (48.3%), PIK3CA (46.6%), and KRAS (20.7%). Pathogenic alterations in PIK3CA, FGFR2, and NBN were associated with worse survival outcomes. Median tumor mutational burden was 3.78 (range, 0-16). All 26 patients with available loss of heterozygosity (LOH) scores had LOH <16%. CONCLUSION: Our study demonstrates encouraging outcomes with bevacizumab and ICI, and SCS in select relapsed OCCC patients. Prospective trials are warranted.

Load frequency stabilization of distinct hybrid conventional and renewable power systems incorporated with electrical vehicles and capacitive energy storage.

Maintaining a power balance between generation and demand is generally acknowledged as being essential to maintaining a system frequency within reasonable bounds. This is especially important for linked renewable-based hybrid power systems (HPS), where disruptions are more likely to occur. This paper suggests a prominent modified "Fractional order-proportional-integral with double derivative (FOPIDD2) controller" as an innovative HPS controller in order to navigate these obstacles. The recommended control approach has been validated in power systems including wind, reheat thermal, solar, and hydro generating, as well as capacitive energy storage and electric vehicle. The improved controller's performance is evaluated by comparing it to regular FOPID, PID, and PIDD2 controllers. Furthermore, the gains of the newly structured FOPIDD2 controller are optimized using a newly intended algorithm terms as squid game optimizer (SGO). The controller's performance is compared to benchmarks such as the grey wolf optimizer (GWO) and jellyfish search optimization. By comparing performance characteristics such as maximum frequency undershoot/overshoot, and steadying time, the SGO-FOPIDD2 controller outperforms the other techniques. The suggested SGO optimized FOPIDD2 controller was analyzed and validated for its ability to withstand the influence of power system parameter uncertainties under various loading scenarios and situations. Without any complicated design, the results show that the new controller can work steadily and regulate frequency with an appropriate controller coefficient.

Frequency regulation of interconnected hybrid power system with Assimilation of electrical vehicles.

Recent widespread connections of renewable energy resource (RESs) in place of fossil fuel supplies and the adoption of electrical vehicles in place of gasoline-powered vehicles have given birth to a number of new concerns. The control architecture of linked power networks now faces an increasingly pressing challenge: tie-line power fluctuations and reducing frequency deviations. Because of their nature and dependence on external circumstances, RESs are analogous to continually fluctuating power generators. Using a fractional order-based frequency regulator, this work presents a new method for improving the frequency regulation in a two-area interconnected power system. In order to deal with the frequency regulation difficulties of the hybrid system integrated with RES, the suggested controller utilizes the modified form of fractional order proportional integral derivative (FOPID) controller known as FOI-PDN controller. The new proposed controllers are designed using the white shark optimizer (WSO), a current powerful bioinspired meta heuristic algorithm which has been motivated by the learning abilities of white sharks when actively hunting in the environment. The suggested FOI-PDN controller's performance was compared to that of various control methodologies such as FOPID, and PID. Furthermore, the WSO findings are compared to those of other techniques such as the salp swarm algorithm, sine cosine algorithm and fitness dependent optimizer. The recommended controller and design approach have been tested and validated at different loading conditions and different circumstances, as well as their robustness against system parameter suspicions. The simulation outcomes demonstrate that the WSO-based tuned FOI-PDN controller successfully reduces peak overshoot by 73.33%, 91.03%, and 77.21% for region-2, region-1, and link power variation respectively, and delivers minimum undershoot of 89.12%, 83.11%, and 78.10% for both regions and tie-line. The obtained findings demonstrate the new proposed controller's stable function and frequency controlling performance with optimal controller parameters and without the requirement for a sophisticated design process.

Return to Sport After Unicompartmental Knee Arthroplasty and Patello-Femoral Arthroplasty.

BACKGROUND: Data on sports/physical activity participation following unicompartmental knee arthroplasty (UKA) and patello-femoral arthroplasty (PFA) is variable and limited. The purpose of this study was to assess participations, outcomes, and limitations in sports following UKA and PFA. METHODS: Patients who underwent UKA and PFA at a single institution from 2015 to 2020 were surveyed on sports participation before and after surgery. Data was correlated with perioperative patient characteristics and outcome scores. Among 776 patients surveyed, 356 (50%) patients responded. Of respondents, 296 (83.1%) underwent UKA, 44 (12.6%) underwent PFA, and 16 (4.5%) underwent both UKA/PFA. RESULTS: Activity participation rates were 86.5, 77.3, and 87.5% five years prior, and 70.9, 61.4, and 75% at one year prior to UKA, PFA, and UKA/PFA, respectively. Return to sports rates were 81.6, 64.7, and 62.3% at mean 4.6 years postoperatively, respectively. The most common activities were recreational walking, swimming, cycling, and golf. Patients returned to a similar participation level for low-impact activities, whereas participation decreased for intermediate- and high-impact activities. Patients participating in activities had higher postoperative Knee Injury and Osteoarthritis Outcome Score Joint Replacement (P < .001), 12-Item Short Form Physical Component Score (P = .045) and Mental Component Score (P = .012). Activity restrictions were reported among 25, 36.4, and 25% of UKA, PFA, and UKA/PFA patients, respectively, and were more commonly self-imposed than surgeon-directed. CONCLUSIONS: Though UKA patients' postoperative sports participation may improve compared to one year preoperatively, participation for patients surgically treated for isolated osteoarthritis is decreased compared to 5 years preoperatively and varies among patient subsets.

The Efficacy of Preoperative Video-Based Opioid Counseling on Postoperative Opioid Consumption After Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.

BACKGROUND: There are myriad strategies to reduce opioid consumption after total knee arthroplasty (TKA). Recent studies have suggested that preoperative counseling may reduce opioid use after a variety of orthopedic procedures. The purpose of this study was to investigate whether preoperative video-based patient education regarding opioid use and abuse reduces opioid consumption after TKA. METHODS: In this prospective randomized controlled trial, patients were randomized before TKA to either receive preoperative video-based counseling or not. Counseling involved a pretaped 5-minute video that educated patients on statistics regarding the "opioid epidemic" and discussed safe use and alternatives to opioids after TKA. There were no significant differences in baseline patient demographics between groups. All patients received a similar multimodal perioperative pain management protocol and completed a daily diary for 2 weeks postoperatively. Diary records measured pain levels using a visual analog score, opioid consumption, side effects experienced, and patient opinion and satisfaction regarding their pain control. RESULTS: Patients in the counseling group consumed significantly less morphine milligram equivalents on postoperative days 0 to 3 (78.8 versus 106.1, P = .020) and in week one postoperatively (129.9 versus 180.7, P = .028), with a trend of less consumption over 2 weeks postoperatively (186.9 versus 239.1, P = .194). There were no significant differences in the number of patients requiring refills, side effects, or daily pain levels between the 2 groups. CONCLUSIONS: This study found significantly decreased opioid consumption within the first week after TKA in patients who received preoperative video counseling.

Assessment of the proteome profile of decellularized human amniotic membrane and its biocompatibility with umbilical cord-derived mesenchymal stem cells.

Extracellular matrix-based bio-scaffolds are useful for tissue engineering as they retain the unique structural, mechanical, and physiological microenvironment of the tissue thus facilitating cellular attachment and matrix activities. However, considering its potential, a comprehensive understanding of the protein profile remains elusive. Herein, we evaluate the impact of decellularization on the human amniotic membrane (hAM) based on its proteome profile, physicochemical features, as well as the attachment, viability, and proliferation of umbilical cord-derived mesenchymal stem cells (hUC-MSC). Proteome profiles of decellularized hAM (D-hAM) were compared with hAM, and gene ontology (GO) enrichment analysis was performed. Proteomic data revealed that D-hAM retained a total of 249 proteins, predominantly comprised of extracellular matrix proteins including collagens (collagen I, collagen IV, collagen VI, collagen VII, and collagen XII), proteoglycans (biglycan, decorin, lumican, mimecan, and versican), glycoproteins (dermatopontin, fibrinogen, fibrillin, laminin, and vitronectin), and growth factors including transforming growth factor beta (TGF-ß) and fibroblast growth factor (FGF) while eliminated most of the intracellular proteins. Scanning electron microscopy was used to analyze the epithelial and basal surfaces of D-hAM. The D-hAM displayed variability in fibril morphology and porosity as compared with hAM, showing loosely packed collagen fibers and prominent large pore areas on the basal side of D-hAM. Both sides of D-hAM supported the growth and proliferation of hUC-MSC. Comparative investigations, however, demonstrated that the basal side of D-hAM displayed higher hUC-MSC proliferation than the epithelial side. These findings highlight the importance of understanding the micro-environmental differences between the two sides of D-hAM while optimizing cell-based therapeutic applications.

3D bio scaffold support osteogenic differentiation of mesenchymal stem cells.

The regeneration of osteochondral lesions by tissue engineering techniques is challenging due to the lack of physicochemical characteristics and dual-lineage (osteogenesis and chondrogenesis). A scaffold with better mechanical properties and dual lineage capability is required for the regeneration of osteochondral defects. In this study, a hydrogel prepared from decellularized human umbilical cord tissue was developed and evaluated for osteochondral regeneration. Mesenchymal stem cells (MSCs) isolated from the umbilical cord were seeded with hydrogel for 28 days, and cell-hydrogel composites were cultured in basal and osteogenic media. Alizarin red staining, quantitative polymerase chain reaction, and immunofluorescent staining were used to confirm that the hydrogel was biocompatible and capable of inducing osteogenic differentiation in umbilical cord-derived MSCs. The findings demonstrate that human MSCs differentiated into an osteogenic lineage following 28 days of cultivation in basal and osteoinductive media. The expression was higher in the cell-hydrogel composites cultured in osteoinductive media, as evidenced by increased levels of messenger RNA and protein expression of osteogenic markers as compared to basal media cultured cell-hydrogel composites. Additionally, calcium deposits were also observed, which provide additional evidence of osteogenic differentiation. The findings demonstrate that the hydrogel is biocompatible with MSCs and possesses osteoinductive capability in vitro. It may be potentially useful for osteochondral regeneration.

Temporal and differential proteomic profile of molecular mediators associated with chronic and acute wound healing.

The underlying pathophysiology of nonhealing chronic wounds is poorly understood due to the changes occurring at the gene level and the complexity arising in their proteomic profile. Here, we elucidated the temporal and differential profile of the normal and diabetic wound-healing mediators along with their interactions and associated pathways. Skin tissues corresponding to normal and diabetic wounds were isolated at Days 0, 3, 6, and 9 representing different healing phases. Temporal gene expression was analyzed by quantitative real-time PCR. Concurrently, differential protein patterns in the wound tissues were identified by Nano LC-ESI-TOF mass spectrometry and later confirmed by Western blot analysis. Gene ontology annotation, protein-protein interaction, and protein pathway analysis were performed using DAVID, PANTHER, and STRING bioinformatics resources. Uniquely identified proteins (complement C3, amyloid beta precursor protein, and cytoplasmic linker associated protein 2) in the diabetic wound tissue implied that these proteins are involved in the pathogenesis of diabetic wound. They exhibit enhanced catalytic activity, trigger pathways linked with inflammation, and negatively regulate wound healing. However, in the normal wound tissue, axin 1, chondroitin sulfate proteoglycan 4, and sphingosine-1-phosphate receptor were identified, which are involved in proliferation, angiogenesis, and remodeling. Our findings demonstrate the correlation between elevated gene expression of tumor necrosis factor-α, interleukin (IL)-1ß, and identified mediators: aryl hydrocarbon receptor nuclear translocator, 5'-aminolevulinate synthase 2, and CXC-family, that inflicted an inflammatory response by activating downstream MAPK, JAK-STAT, and NF-κB pathways. Similarly, in normal wound tissue, the upregulated IL-4 and hepatocyte growth factor levels in conjunction with the identified proteins, serine/threonine-protein kinase mTOR and peroxisome proliferator-activated receptor gamma, played a significant role in the cellular response to platelet-derived growth factor stimulus, dermal epithelialization, and cell proliferation, processes associated with the repair mechanism. Furthermore, Western blot analysis indicated elevated levels of inflammatory markers and reduced levels of proliferative and angiogenic factors in the diabetic wound.

Stabilization and tracking control of underactuated ball and beam system using metaheuristic optimization based TID-F and PIDD2-PI control schemes.

In this paper, we propose two different control strategies for the position control of the ball of the ball and beam system (BBS). The first control strategy uses the proportional integral derivative-second derivative with a proportional integrator PIDD2-PI. The second control strategy uses the tilt integral derivative with filter (TID-F). The designed controllers employ two distinct metaheuristic computation techniques: grey wolf optimization (GWO) and whale optimization algorithm (WOA) for the parameter tuning. We evaluated the dynamic and steady-state performance of the proposed control strategies using four performance indices. In addition, to analyze the robustness of proposed control strategies, a comprehensive comparison has been performed with a variety of controllers, including tilt integral-derivative (TID), fractional order proportional integral derivative (FOPID), integral-proportional derivative (I-PD), proportional integral-derivative (PI-D), and proportional integral proportional derivative (PI-PD). By comparing different test cases, including the variation in the parameters of the BBS with disturbance, we examine step response, set point tracking, disturbance rejection analysis, and robustness of proposed control strategies. The comprehensive comparison of results shows that WOA-PIDD2-PI-ISE and GWO-TID-F- ISE perform superior. Moreover, the proposed control strategies yield oscillation-free, stable, and quick response, which confirms the robustness of the proposed control strategies to the disturbance, parameter variation of BBS, and tracking performance. The practical implementation of the proposed controllers can be in the field of under actuated mechanical systems (UMS), robotics and industrial automation. The proposed control strategies are successfully tested in MATLAB simulation.