Intrathecal ropivacaine versus bupivacaine in a non-obstetric population- A meta-analysis and trial sequential analysis.

Background and Aims: Intrathecal bupivacaine is used for anaesthesia and analgesia but is associated with hypotension. Ropivacaine is an alternative drug that may have fewer cardiotoxic and neurotoxic events. This meta-analysis investigated whether intrathecal ropivacaine is associated with reduced hypotension as compared to bupivacaine. Methods: The meta-analysis is registered in the International Prospective Register of Systematic Reviews (PROSPERO). The databases PubMed, Cinahl Plus, Google Scholar, and Scopus were searched, and papers from January 1980 to January 2023 were deemed eligible and filtered using predetermined inclusion and exclusion criteria. The primary outcome was the incidence of hypotension. Secondary outcomes were the duration of sensory block, duration of motor block, incidence of bradycardia, ephedrine usage, and duration of analgesia. Jadad scores were used to evaluate the quality of the papers. RevMan statistical software® utilised inverse variance and a random effect model to calculate the standardised mean difference with 95% confidence intervals for continuous variables and the Mantel-Haenszel test and the random effect model to calculate the odds ratio for dichotomous variables. Results: Thirty-three papers, including 2475 patients in total, were included. The Jadad score was between 1 and 5. The incidence of hypotension was significantly higher with intrathecal bupivacaine than with ropivacaine (P = 0.02). The duration of sensory block (P < 0.001) and motor block (P < 0.001) was prolonged with intrathecal bupivacaine. The duration of analgesia favoured intrathecal bupivacaine (P = 0.003). Conclusion: Intrathecal ropivacaine has a reduced incidence of hypotension and a reduced duration of sensory block compared to bupivacaine.

The analgesic effects of bilateral superficial cervical plexus block in thyroid surgery: A systematic review and meta-analysis.

Background and Aims: Thyroid surgery is moderately painful, and many techniques to reduce postoperative pain have been studied. Regional techniques are a part of multimodal analgesia employed for various surgical cases. Bilateral superficial cervical plexus block (BSCPB) is a commonly used regional anaesthesia technique for analgesia for thyroid surgery. A previous meta-analysis by this group had left questions about some facets of the technique, to which further trials have contributed. Methods: The systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO) CRD42022315499. It is an update to a previously published paper in 2018. An updated systematic search, critical appraisal, and analysis of clinical trials were performed. Trials investigating preoperative or postoperative BSCPB compared to control in patients undergoing thyroid surgery were included in the search. The primary outcome was postoperative opioid consumption. The secondary outcomes were the duration of analgesia (time to request of analgesia), Visual Analogue Scale (VAS) pain scores at 0, 4, 12, and 24 h, postoperatively, rates of postoperative nausea and vomiting (PONV), postoperative rescue analgesic consumption, and intraoperative morphine use. Results: A total of 31 studies and 2,273 patients were included in this analysis. BSCPB significantly reduced post-thyroidectomy opioid consumption (P < 0.001). Additionally, the duration of analgesia was prolonged following BSCPB. VAS scores for 24 h (postoperatively), intraoperative morphine use, and rescue analgesia (postoperatively) remained significantly lower in patients who received BSCPB. There was also a statistically significant reduction in PONV (P = 0.02). Conclusion: BSCPB offers superior postoperative analgesia with a reduction in opioid use, reduction in PONV, and improvement in VAS scores.

An extracellular vesicular mutant KRAS-associated protein complex promotes lung inflammation and tumor growth.

Extracellular vesicles (EVs) contain more than 100 proteins. Whether there are EVs proteins that act as an 'organiser' of protein networks to generate a new or different biological effect from that identified in EV-producing cells has never been demonstrated. Here, as a proof-of-concept, we demonstrate that EV-G12D-mutant KRAS serves as a leader that forms a protein complex and promotes lung inflammation and tumour growth via the Fn1/IL-17A/FGF21 axis. Mechanistically, in contrast to cytosol derived G12D-mutant KRAS complex from EVs-producing cells, EV-G12D-mutant KRAS interacts with a group of extracellular vesicular factors via fibronectin-1 (Fn1), which drives the activation of the IL-17A/FGF21 inflammation pathway in EV recipient cells. We show that: (i), depletion of EV-Fn1 leads to a reduction of a number of inflammatory cytokines including IL-17A; (ii) induction of IL-17A promotes lung inflammation, which in turn leads to IL-17A mediated induction of FGF21 in the lung; and (iii) EV-G12D-mutant KRAS complex mediated lung inflammation is abrogated in IL-17 receptor KO mice. These findings establish a new concept in EV function with potential implications for novel therapeutic interventions in EV-mediated disease processes.

Multiscale Modeling of Sintering-Driven Conductivity in Large Nanowire Ensembles.

Thermally driven sintering is widely used to enhance the conductivity of metal nanowire (NW) ensembles in printed electronics applications, with rapid nonisothermal sintering being increasingly employed to minimize substrate damage. The rational design of the sintering process and the NW morphology is hindered by a lack of mechanistically motivated and computationally efficient models that can predict sintering-driven neck growth between NWs and the resulting change in ensemble conductivity. We present a de novo modeling framework that, for the first time, links rotation-regulated nanoscale neck growth observed in atomistic simulations to continuum conductivity evolution in inch-scale NW ensembles via an analytical neck growth model and master curve formulations of neck growth and resistivity. This framework is experimentally validated against the emergent intense pulsed light-sintering process for Ag NWs. An ultralow computational effort of 0.2 CPU-h is achieved, 4-10 orders of magnitude reduction as compared to the state of the art. We show that the inherent local variation in the relative NW orientation within an ensemble drives significant junction-specific differences in neck growth kinetics and junction resistivity. This goes beyond the conventional assumption that the neck growth kinetics is the same at all the NW junctions in an ensemble, with significant implications on how nanoscale neck growth affects ensemble-scale conductivity. Through its low computational time, easy and rapid recalibration, and experimental relevance, our framework constitutes a much-needed foundational enabler for a priori design of the sintering process and the NWs.

Utility of the END-IT Score to Predict the outcome of Childhood Status Epilepticus: A Retrospective Cohort Study.

INTRODUCTION: Scoring systems to predict outcomes in pediatric status epilepticus (SE) are limited. We sought to assess usefulness of the END-IT score in pediatric SE. METHODOLOGY: We conducted a retrospective study at a tertiary hospital in New Delhi, India. Children aged 1 month-18 years who presented with seizure for ≥5 min/actively convulsing to emergency were enrolled. END-IT score was calculated and correlated with outcome at discharge using Pediatric Overall Performance Category (POPC) scale, in-hospital mortality, and progression to refractory and super-refractory SE (SRSE). RESULTS: We enrolled 140 children (mean age 5.8 years; 67.1% males). Seven children died and 15 had unfavorable outcomes. The predictive accuracy of END-IT at a cutoff of > 2: for unfavorable outcome (POPC score ≥3) was: sensitivity 0.73 (95% CI: 0.45-0.92), specificity 0.94 (95% CI: 0.89-0.98), PPV 0.61 (95% CI: 0.36-0.83), NPV 0.97 (95% CI: 0.92-0.99), positive likelihood ratio (13.09), F1 score (0.666); for death: sensitivity 0.86 (95% CI: 0.42-0.99), specificity 0.91 (95% CI: 0.85-0.95), PPV 0.33 (95% CI: 0.13-0.59), NPV 0.99 (95% CI: 0.96-1.00), F1 score (0.48); for RSE: sensitivity 0.80 (95%CI: 0.28-0.99), specificity 0.90 (95% CI: 0.83-0.94), PPV 0.22 (95% CI: 0.06-0.48) NPV 0.99 (95% CI: 0.96-1.00), F1 score (0.35); for SRSE: sensitivity 0.67 (95% CI: 0.22-0.96) specificity 0.75 (95% CI: 0.66-0.82), PPV 0.22 (95% CI: 0.06-0.48) NPV 0.98 (95% CI: 0.94-0.99), F1 score (0.33). CONCLUSION: We demonstrate utility of the END-IT score to predict short-term outcomes as well as progression to refractory and SRSE for the first time among children with SE.

Cardioprotective effects of azilsartan compared with that of telmisartan on an in vivo model of myocardial ischemia-reperfusion injury.

Azilsartan is found to be more potent than other angiotensin receptor blockers in reducing blood pressure. However, its effect on the heart following myocardial infarction remains to be established. For the first time, we investigated the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonistic and cardioprotective properties of azilsartan. Computational modeling studies of interactions between azilsartan and PPAR-γ revealed azilsartan as an agonist of PPAR-γ and showed the mechanism of azilsartan in cardioprotection. Our study compared the cardioprotective potential of telmisartan to that of azilsartan in a murine model of myocardial ischemia-reperfusion injury by comparing their antioxidant, ant apoptotic, anti-inflammatory, mitogen-activated protein kinase (MAPK)-modulating ability, and PPAR-γ agonistic activity. Male Wistar rats were grouped into four to receive vehicle (dimethyl sulfoxide [0.05%] 2 ml/kg) telmisartan (10 mg/kg p.o.), azilsartan (10 mg/kg p.o.) or azilsartan with specific PPAR-γ blocker, GW 9662 for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Telmisartan and azilsartan pretreatment significantly nearly normalized cardiac parameters and preserved structural changes. Both drugs inhibited oxidative burst, inflammation, as well as cell death by modulating apoptotic protein expression along with reduction in 4',6-diamidino-2-phenylindole/terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. An increment in pro-survival kinase ERK paralleled with a reduction in p38 and JNK was also revealed by MAPK pathway studies, after administration of these drugs. Interestingly, the aforementioned changes induced by both drugs were reversed by administration of the specific PPAR-γ antagonist, GW9662. However, we found that azilsartan upregulated PPAR-γ to a lesser extent as compared to telmisartan and the latter may be preferred in hypertensive patients at risk of myocardial infarction.

The molecular mechanism involved in cardioprotection by the dietary flavonoid fisetin as an agonist of PPAR-γ in a murine model of myocardial infarction.

The methodology exploring the cardioprotective potential of the flavonoid Fisetin through its ability to modulate PPAR-γ was unraveled in the present study. Computational modelling through molecular docking based binding study of interactions between Fiestin and PPAR-γ revealed the potential role of Fisetin as an agonist of PPAR-γ. A murine model of cardiac ischemia-reperfusion injury was used to explore this further. Male Wistar Rats were randomly assigned to five groups. Fisetin (20 mg/kg; p. o) was administered for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Fisetin pretreatment upregulated the expression of PPAR-γ in heart tissue significantly Cardioprotection was assessed by measurement of hemodynamic parameters, infarct size, ELISA for oxidative stress, immunohistochemistry and TUNEL assay for apoptosis, and western blot analysis for MAPK proteins and inflammation. PPAR-γ activation by fisetin led to significantly reduced infarct size, suppression of oxidative stress, reduction of cardiac injury markers, alleviation of inflammation, and inhibition of apoptosis The MAPK-based molecular mechanism showed a rise in a key prosurvival kinase, ERK1/ERK2 and suppression of JNK and p38 proteins. The aforementioned beneficial findings of fisetin were reversed on the administration of a specific antagonist of PPAR-γ. In conclusion, through our experiments, we have proved that fisetin protects the heart against ischemia-reperfusion injury and the evident cardioprotection is PPAR-γ dependant. In conclusion, our study has revealed a prime mechanism involved in the cardioprotective effects of fisetin. Hence, Fisetin may be evaluated in further clinical studies as a cardioprotective agent in patients undergoing reperfusion interventions.

Corrigendum to "Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury".

[This corrects the article DOI: 10.1155/2016/7580731.].

Oral Vitamin D Supplementation to Mothers During Lactation-Effect of 25(OH)D Concentration on Exclusively Breastfed Infants at 6 Months of Age: A Randomized Double-Blind Placebo-Controlled Trial.

Background: Exclusively breastfed infants are at risk of vitamin D deficiency. Objective: To find out proportion of exclusively breastfed infants having serum 25(OH)D concentration <11 ng/mL at 6 months of age with or without oral supplementation of vitamin D3 to lactating mothers. Methods: Randomized placebo-controlled study included 132 mothers and infants divided into two groups. Mothers received either vitamin D3 60,000 IU between 24 and 48 hours postpartum and at 6, 10, and 14 weeks amounting to 240,000 IU of vitamin D3 or placebo. Serum 25(OH)D concentration in the mothers was measured at recruitment and that of infants, at birth and 6 months. Infants were evaluated for rickets at 6 months. Findings: Total 114 mother-infant dyads followed. Subjects in both groups were comparable in basic characteristics. At 6 months of age, serum 25(OH)D concentration in infants was 18.93 (5.12) ng/mL in the intervention group and 6.43 (3.76) ng/mL in the control group (mean difference = 12.5; 95% CI = 10.80-14.17; p < 0.001) and vitamin D deficiency and insufficiency was corrected in 93.1% and 38% infants, respectively, in the intervention group. There was no change in the vitamin D status of infants in the control group. In 60.3% infants (RR = 0.519; 95% CI = -0.485 to 0.735) of the intervention group 25(OH)D concentration was <20 ng/mL at 6 months of age. Six infants in the control group suffered from biochemical rickets. Radiological rickets developed in one infant in the intervention group and two infants in the control group. Conclusion: Serum 25(OH)D concentration of exclusively breastfed infants rise significantly when mothers are orally supplemented with 240,000 IU of vitamin D3 during lactation in comparison with the infants of unsupplemented mothers with 94.6% and 48.1% reduction in the risk of vitamin D deficiency and insufficiency, respectively, at 6 months of age.

Author Correction: Temperature, Crystalline Phase and Influence of Substrate Properties in Intense Pulsed Light Sintering of Copper Sulfide Nanoparticle Thin Films.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Role of Metformin, Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists, and Orlistat based Multidrug Therapy in Glycemic Control, Weight Loss, and Euglycemia in Diabesity: A Real-World Experience.

BACKGROUND: This study evaluated the real-world weight loss and glycemic outcomes of multidrug therapy (MDT) according to various combinations of metformin, sodium-glucose cotransporter -2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor analogs (GLP1a), and orlistat in diabesity. METHODS: Data retrospectively captured from medical records of 2 different centers in New Delhi for patients >35 years-age having prediabetes/diabetes and on at least any one of the 4 above medications with >6-months follow-up was analyzed. RESULTS: In total, 5,336 patient records were screened; 2,442 with prediabetes/diabetes were considered; 1,509 patients who fulfilled all criteria were analyzed. Use of metformin, SGLT2i, sulfonylureas, DPP4i, pioglitazone, orlistat, and GLP1a was 85.35%, 74.95%, 68.32%, 60%, 39.16%, 9.08%, and 4.17%, respectively. However, 365, 970, and 104 patients were on one of 4 concerned medications (Group-1; 24.18%), dual MDT (Group-2; 64.28%), and triple/quadruple MDT (Group-3; 6.89%). Metformin with SGLT2i was most commonly used dual MDT (94.12%). Analysis according to weight-loss quartiles from 558 patients showed 6.9 kg weight-loss in the highest quartile. People losing maximum weight were significantly younger; had higher use of metformin, SGLT2i, GLP1, orlistat, and lower pioglitazone use; greatest HbA1c reduction (-1.3 vs. -0.3; quartile-1 vs. quartile -4; P < 0.001); and significantly higher occurrence of HbA1c<5.7% (16.8% vs. 6.29%; quartile-1 vs. 4; P < 0.001). Patients in Group-3 had the highest baseline BMI and maximum weight loss with highest number of patients with HbA1c<5.7% (19.44% vs. 10.34%; Group-3 vs. Group-1; P < 0.001). CONCLUSION: Greater weight loss with HbA1c reduction along with a greater number of patients attaining HbA1c <5.7% highlights that MDT is the way forward to tackle diabesity in India.

Fisetin attenuates isoproterenol-induced cardiac ischemic injury in vivo by suppressing RAGE/NF-κB mediated oxidative stress, apoptosis and inflammation.

BACKGROUND: The therapeutic options for the reducing the damage caused by myocardial ischemia are limited and not devoid of adverse effects. The role of the flavanoid, fisetin, predominantly found in strawberry and apple, is yet to be explored in the heart. STUDY DESIGN: Male Wistar rats (n = 48) were administered fisetin (10, 20 & 40 mg/kg/day, orally) or vehicle for 28 days while ISO, 85 mg/kg, subcutaneously, was also administered at 24 h interval on the 27th and 28th day. On the 29th day, rats were anaesthetized and right carotid artery was cannulated to record hemodynamic parameters. Subsequently, blood sample was collected and heart was removed to evaluate various parameters. RESULTS: Fisetin at doses of 10 and 20 mg/kg reversed ISO induced detrimental alterations in blood pressure and left ventricular pressures and reduced the myocardial injury markers CK-MB and LDH in the serum. These findings were supported by amelioration of ISO induced histological and ultrastructural damage by fisetin. The disequilibrium in the levels of pro and anti oxidants in the myocardial tissue caused by ISO was also normalized Furthermore, apoptosis was evident from enhanced DNA fragmentation and raised pro-apoptotic proteins (bax, caspase-3, cytochrome-c) as well as suppressed anti-apoptotic protein (Bcl-2) in case of ISO treatment which again was reversed by fisetin. A molecular mechanism for this protection was elucidated as downregulation of RAGE and NF-κB However fisetin at 40 mg/kg revealed a deteriorating effect which was similar to ISO group of rats. CONCLUSION: Hence, through our study, the role of fisetin in cardioprotection has been uncovered via a molecular pathway.

Shape-Tuned Junction Resistivity and Self-Damping Dynamics in Intense Pulsed Light Sintering of Silver Nanostructure Films.

Concurrently reducing processing temperature, electrical resistance, and material cost with scalable fabrication capabilities is critical for conductive elements of flexible and planar electronics. Intense pulsed light sintering (IPL) of mixed dissimilar-shape conductive nanostructures may achieve this goal. However, this potential is hindered by knowledge gaps on how dissimilarity in nanostructure shape affects interparticle neck growth kinetics in general and the self-damping coupling between neck growth and optical absorption in IPL. We study these phenomena for IPL of mixed Ag nanowires (NWs, 40 nm diameter, 100-200 µm length) and nanospheres (NSs, 40 nm diameter), both experimentally and by linking molecular dynamics simulations with optical modeling. An optimal 50:50 mixing ratio lowers resistivity (5.59 µΩ·cm) and peak temperatures (250-150 °C) relative to pure NS films and reduces material costs relative to pure NW films with similar resistivity, in 2.5 s of IPL. The drop in peak temperatures in consecutive optical pulses reduces with greater NW content. Sintering-induced dislocation generation drives higher neck growth at NW-NS and NW-NW interfaces and anisotropic neck growth at NW-NS interfaces. This indicates that when NWs are introduced into NS films, along with lesser number of interfacial contact points, an inherent reduction in sintering-induced junction resistivity plays a major role in reducing film resistivity. The self-damping coupling and optical absorption, which drive temperature evolution in IPL, are tunable by nanostructure shape. The introduction of NWs into a NS ensemble reduces the dependence of optical absorption on neck growth. We discuss how these insights elucidate a set of physical phenomena that can guide the choice of dissimilar shaped nanostructures to concurrently reduce resistivity and temperatures in IPL and other sintering processes.

Rapid Pulsed Light Sintering of Silver Nanowires on Woven Polyester for personal thermal management with enhanced performance, durability and cost-effectiveness.

Fabric-based personal heating patches have small geometric profiles and can be attached to selected areas of garments for personal thermal management to enable significant energy savings in built environments. Scalable fabrication of such patches with high thermal performance at low applied voltage, high durability and low materials cost is critical to the widespread implementation of these energy savings. This work investigates a scalable Intense Pulsed Light (IPL) sintering process for fabricating silver nanowire on woven polyester heating patches. Just 300 microseconds of IPL sintering results in 30% lesser electrical resistance, 70% higher thermal performance, greater durability (under bending up to 2 mm radius of curvature, washing, humidity and high temperature), with only 50% the added nanowire mass compared to state-of-the-art. Computational modeling combining electromagnetic and thermal simulations is performed to uncover the nanoscale temperature gradients during IPL sintering, and the underlying reason for greater durability of the nanowire-fabric after sintering. This large-area, high speed, and ambient-condition IPL sintering process represents an attractive strategy for scalably fabricating personal heating fabric-patches with greater thermal performance, higher durability and reduced costs.

Modeling nanoscale temperature gradients and conductivity evolution in pulsed light sintering of silver nanowire networks.

Sintering of metal nanowire (NW) networks on transparent polymers is an emerging approach for fabricating transparent conductive electrodes used in multiple devices. Pulsed light sintering is a scalable sintering process in which large-area, broad-spectrum xenon lamp light causes rapid NW fusion to increase network conductivity, while embedding the NWs in the polymer to increase mechanical robustness. This paper develops a multiphysical approach for predicting evolution of conductivity, NW fusion and nanoscale temperature gradients on the substrate during pulsed light sintering of silver NWs on polycarbonate. Model predictions are successfully validated against experimentally measured temperature and electrical resistance evolution. New insight is obtained into the diameter-dependent kinetics of NW fusion and nanoscale temperature gradients on the substrate, which are difficult to obtain experimentally. These observations also lead to the understanding that NW embedding in intense pulsed light sintering (IPL) can occur below the glass transition temperature of the polymer, and to a new differential thermal expansion-based mechanism of NW embedding during IPL. These insights, and the developed model, create a framework for physics-guided choice of NWs, substrate and process parameters to control conductivity and prevent substrate damage during the process.

Temperature, Crystalline Phase and Influence of Substrate Properties in Intense Pulsed Light Sintering of Copper Sulfide Nanoparticle Thin Films.

Intense Pulsed Light sintering (IPL) uses pulsed, visible light to sinter nanoparticles (NPs) into films used in functional devices. While IPL of chalcogenide NPs is demonstrated, there is limited work on prediction of crystalline phase of the film and the impact of optical properties of the substrate. Here we characterize and model the evolution of film temperature and crystalline phase during IPL of chalcogenide copper sulfide NP films on glass. Recrystallization of the film to crystalline covellite and digenite phases occurs at 126 °C and 155 °C respectively within 2-7 seconds. Post-IPL films exhibit p-type behavior, lower resistivity (~10-3-10-4 Ω-cm), similar visible transmission and lower near-infrared transmission as compared to the as-deposited film. A thermal model is experimentally validated, and extended by combining it with a thermodynamic approach for crystal phase prediction and via incorporating the influence of film transmittivity and optical properties of the substrate on heating during IPL. The model is used to show the need to a-priori control IPL parameters to concurrently account for both the thermal and optical properties of the film and substrate in order to obtain a desired crystalline phase during IPL of such thin films on paper and polycarbonate substrates.

Corrigendum: Seabuckthorn Pulp Oil Protects against Myocardial Ischemia-Reperfusion Injury in Rats through Activation of Akt/eNOS.

[This corrects the article DOI: 10.3389/fphar.2016.00155.].

Febuxostat Modulates MAPK/NF-κBp65/TNF-α Signaling in Cardiac Ischemia-Reperfusion Injury.

Xanthine oxidase and xanthine dehydrogenase have been implicated in producing myocardial damage following reperfusion of an occluded coronary artery. We investigated and compared the effect of febuxostat and allopurinol in an experimental model of ischemia-reperfusion (IR) injury with a focus on the signaling pathways involved. Male Wistar rats were orally administered vehicle (CMC) once daily (sham and IR + control), febuxostat (10 mg/kg/day; FEB10 + IR), or allopurinol (100 mg/kg/day; ALL100 + IR) for 14 days. On the 15th day, the IR-control and treatment groups were subjected to one-stage left anterior descending (LAD) coronary artery ligation for 45 minutes followed by a 60-minute reperfusion. Febuxostat and allopurinol pretreatment significantly improved cardiac function and maintained morphological alterations. They also attenuated oxidative stress and apoptosis by suppressing the expression of proapoptotic proteins (Bax and caspase-3), reducing TUNEL-positive cells, and increasing the level of antiapoptotic proteins (Bcl-2). The MAPK-based molecular mechanism revealed suppression of active JNK and p38 proteins concomitant with the rise in ERK1/ERK2, a prosurvival kinase. Additionally, a reduction in the level of inflammatory markers (TNF-α, IL-6, and NF-κB) was also observed. The changes observed with febuxostat were remarkable in comparison with those observed with allopurinol. Febuxostat protects relatively better against IR injury than allopurinol by suppressing inflammation and apoptosis mediating the MAPK/NF-κBp65/TNF-α pathway.

Molecular Pathways Involved in the Amelioration of Myocardial Injury in Diabetic Rats by Kaempferol.

There is growing evidence that chronic hyperglycemia leads to the formation of advanced glycation end products (AGEs) which exerts its effect via interaction with the receptor for advanced glycation end products (RAGE). AGE-RAGE activation results in oxidative stress and inflammation. It is well known that this mechanism is involved in the pathogenesis of cardiovascular disease in diabetes. Kaempferol, a dietary flavonoid, is known to possess antioxidant, anti-apoptotic, and anti-inflammatory activities. However, little is known about the effect of kaempferol on myocardial ischemia-reperfusion (IR) injury in diabetic rats. Diabetes was induced in male albino Wistar rats using streptozotocin (70 mg/kg; i.p.), and rats with glucose level >250 mg/dL were considered as diabetic. Diabetic rats were treated with vehicle (2 mL/kg; i.p.) and kaempferol (20 mg/kg; i.p.) daily for a period of 28 days and on the 28th day, ischemia was produced by one-stage ligation of the left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed and the heart tissue was processed for biochemical, morphological, and molecular studies. Kaempferol pretreatment significantly reduced hyperglycemia, maintained hemodynamic function, suppressed AGE-RAGE axis activation, normalized oxidative stress, and preserved morphological alterations. In addition, there was decreased level of inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and NF-κB), inhibition of active c-Jun N-terminal kinase (JNK) and p38 proteins, and activation of Extracellular signal regulated kinase 1/2 (ERK1/2) a prosurvival kinase. Furthermore, it also attenuated apoptosis by reducing the expression of pro-apoptotic proteins (Bax and Caspase-3), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells, and increasing the level of anti-apoptotic protein (Bcl-2). In conclusion, kaempferol attenuated myocardial ischemia-reperfusion injury in diabetic rats by reducing AGE-RAGE/ mitogen activated protein kinase (MAPK) induced oxidative stress and inflammation.

Airway Complications of Total Artificial Heart.

The total artificial heart is the mechanical device which is used as a bridge to the heart transplant in patients with biventricular failure. Due to the mechanical nature of the device, patients receiving total artificial heart (TAH) require to be on anticoagulation therapy. Hemorrhage and coagulopathy are few of the known complications of TAH.