Empowering Little Fighters: Post-Cardiotomy Pediatric ECMO and the Journey to Recovery.

INTRODUCTION: Extra Corporeal Membrane Oxygenation (ECMO) has long been used for cardiorespiratory support in the immediate post-paediatric cardiac surgery period with a 2-3% success as per the ELSO registry. Success in recovery depends upon the optimal delivery of critical care to paediatric patients and a comprehensive healthcare team. METHODOLOGY: The survival benefit of children placed on central veno arterial (VA) ECMO following elective cardiac surgeries for congenital heart disease (n = 672) was studied in a cohort of 29 (4.3%) cases from the period of Jan 2018 to Dec 2022 in our cardiac surgical centre. Indications for placing these patients on central VA ECMO included inability to wean from cardiopulmonary bypass (CPB), low cardiac output syndrome, severe pulmonary arterial hypertension, significant bleeding, anaphylaxis, respiratory failure and severe pulmonary edema. RESULTS: The mean time to initiation of ECMO was less than 5 h and the mean duration of ECMO support was 56 h with a survival rate of 58.3%. Amongst perioperative complications, sepsis and arrhythmia on ECMO were found to be negatively associated with survival. Improvements in the pH, PaO2 levels and serum lactate levels after initiation of ECMO were associated with survival benefits. CONCLUSION: The early initiation of ECMO for paediatric cardiotomies could be a beacon of hope for families and medical teams confronting these challenging situations. Improvement in indicators of adequate perfusion and ventricular recoveries like pH and serum lactate and absence of arrhythmia and sepsis are associated with good outcomes.

Neuroplastin splice variants Np55 and Np65: Who is doing the job in macrophages?

Neuroplastin, a paralog of CD147/Basigin, is known as a neuronal cell adhesion molecule and as an auxiliary subunit of plasma membrane calcium ATPases in both neurons and adaptive immune cells. Recently, an interesting study by Ren et al. (2022) provided evidence for an important role of neuroplastin in macrophages during bacterial infection. Here, we critically discuss one aspect of this study, the assignment of this role to Np65 as one of two prominent splice variants of neuroplastin.

Non-analgesic benefits of combined thoracic epidural analgesia with general anesthesia in on-pump pediatric cardiac surgery: A prospective observational study.

Background: The use of thoracic epidural analgesia in infants and children could attenuate the stress response and thereby improve the outcomes associated with cardiac surgery. Methods: This study is a prospective observational study conducted on 118 patients admitted for cardiac surgery. All patients received thoracic epidural analgesia. Laboratory investigations including inflammatory markers, markers for different organ functions, and intensive care unit parameters were collected at different time points (preoperative, immediate postoperative, on day 1, and day 2). Results: Inflammatory markers such as IL6, IL8, and metabolic response as measured by serum cortisol and blood sugar were significantly high in the immediate postoperative period, which later stabilized in the next 48 h. There was also a sharp increase in the anti-inflammatory marker IL-10 in an immediate postoperative period, which settled later on but continued to be higher than baseline in the next 48 h. All these markers showed lower values when compared to published literature. The baseline renal oxygen saturation using near infrared spectroscopy (NIRS) value in our study was 59.3 + 19, which increased to 76.4 + 12.7 on day 2. Serum neutrophil gelatinase associated lipocalin (NGAL) remained well below normal levels in the perioperative period. PF (pO2/FiO2) ratio and pO2 consistently improved postoperatively with the maximum on day 2. The median mechanical ventilation (MV) duration was 18 h, and the mean length of stay that included intensive care unit stay was 12 days. No epidural-related adverse events were noted. Conclusions: Apart from good analgesia, patients receiving thoracic epidural analgesia displayed a reduction in perioperative stress, superior postoperative glycemic control, reduction in inflammatory markers, postoperative acute kidney injury, and pulmonary complications.

50-years journey of heart transplant.

Heart transplant is an established modality for the treatment of heart disease refractory to medical therapy. The last 50 years have seen the evolution of immune suppression therapy and standardization of protocols which have significantly improved outcomes following cardiac transplants. Donor availability is the main limiting factor and has restricted the number of heart transplants worldwide. Simultaneously, left ventricular assist devices have evolved to provide a "bridge" for recovery and transplant and alternatively as destination therapy to those waiting for the availability of a donor. This review article provides an overview of the current status of heart transplants after half a century and specific issues pertaining to our country.

Ambulatory milrinone therapy as a bridge to heart transplantation.

Inotrope therapy for patients with advanced heart failure awaiting a heart transplant or ventricular assist device has been reported to facilitate hospital discharge. We report the case of a 46-year-old man with advanced heart failure (Stage D), initially found unsuitable for a heart transplant due to high pulmonary vascular resistance (PVR) was placed on ambulatory Milrinone therapy leading to significant improvement in PVR. He underwent a successful orthotopic heart transplant.

Low-Dose vasopressin and renal perfusion in pediatric cardiac surgery.

Background: Congenital heart surgeries are associated with post-bypass renal and cardiac dysfunctions. The use of low-dose vasopressin has been found to be beneficial in adult cardiac surgeries. Objective: To assess the hemodynamic and renal effects of patients undergoing on-pump pediatric cardiac surgery under general anesthesia (GA) with low-dose vasopressin infusion. Design: Prospective randomized controlled study. Setting: Operation room and ICU, tertiary care teaching hospital. Patients: Fifty-five pediatric cardiac patients undergoing repair for congenital heart diseases (CHD). Interventions: Low-dose vasopressin infusion in the study group and placebo in the control group. Measurements and Main Results: Renal near-infrared spectroscopy (NIRS), serum NGAL, and inflammatory mediators-IL6 and IL8 along with other renal and hemodynamic parameters in the perioperative period were recorded. Diastolic blood pressure (DBP) and cardiac index were significantly higher in the vasopressin group. Inflammatory markers were significantly high in the immediate postoperative period in all patients which later stabilized in the next 48 h but showed similar trends in both groups. Low-dose vasopressin infusion did not improve either renal perfusion or function. The duration of mechanical ventilation and length of hospital stay, the incidence of AKI development, and transfusion requirements were marginally lower in the vasopressin group, although not significant. Conclusion: Low-dose vasopressin infusion improved hemodynamics and showed a decreased incidence of complications. However, it failed to show any benefit of renal function and overall outcome in pediatric cardiac surgery.

High-frequency oscillatory ventilation for respiratory failure after congenital heart surgery: a retrospective analysis.

INTRODUCTION: Pulmonary complications such as acute respiratory distress syndrome and refractory respiratory failure have been major causes of morbidity and mortality after cardiac surgery in children. Patients are usually transitioned to either high-frequency oscillatory ventilation (HFOV) or extracorporeal membrane oxygenation (ECMO) as "salvage therapy" when the maximal medical management and controlled mechanical ventilation (CMV) become ineffective. MATERIAL AND METHODS: A retrospective review of paediatric patients who underwent congenital heart surgery and developed cardiorespiratory failure during their stay in a paediatric cardiac ICU, refractory to maximal CMV, was performed in the study. The outcomes assessed were respiratory variables such as SpO 2 , RR, oxygenation index (OI), P/F ratio, and ABG parameters in CMV and HFOV as predictors of survival. RESULTS: Twenty-four children with cardiorespiratory failure were candidates for a transition to either HFOV ( n = 15) or VA ECMO ( n = 9) for refractory hypoxaemia; of these 24 patients, 13 (54.16%) survived. PaO2 showed a significant improvement in the survivors (P = 0.03). Improvement in the PaO 2 /FiO 2 (P/F ratio) after initiation of HFOV was associated with survival ( P < 0.001). pH, PaCO 2 , HCO 3 , FiO 2 , Paw, RR/Amp, SpO 2 , and OI also showed improvements in survivors but these were not statistically significant. The HFOV survivors had longer mechanical ventilation and ICU stay than non-survivors ( P = 0.13). CONCLUSIONS: HFOV was associated with improved gas exchange for paediatric patients who developed post-cardiac surgery refractory respiratory failure. HFOV can be considered as rescue therapy where ECMO has major financial implications.

Near-IR absorbing 1,1,4,4-tetracyanobutadiene-functionalized phenothiazine sulfones.

Triphenylamine (TPA) substituted π-conjugated chromophores TPA1-TPA5 were designed and synthesized via Pd-catalysed Sonogashira cross-coupling followed by [2 + 2] cycloaddition-retroelectrocyclization (CA-RE) reactions. The effects of acceptor 1,1,4,4-tetracyanobutadiene (TCBD) and cyclohexa-2,5-diene-1,4-diylidene-expanded TCBD (DCNQ) units in the photophysical studies and the HOMO-LUMO energy levels of the phenothiazine sulfones TPA1-TPA5 were evaluated. The absorption spectra of chromophores TPA4 and TPA5 show a significant change due to the incorporation of DCNQ units, resulting in bathochromically shifted broad absorption in the NIR region. The photophysical studies revealed that DCNQ-based chromophores TPA4 and TPA5 have a better D-A interaction than the TCBD functionalized TPA2 and TPA3. Density functional theory calculations and electrochemical studies were performed to examine the molecular geometry and frontier energy levels of the sulfone-based chromophores. Systematic structural modification of the chromophore TPA1 modulated the electrochemical properties and successively tuned the energy gaps for TPA2-TPA5. The theoretically estimated HOMO-LUMO gaps for TPA1-TPA5 exhibit good agreement with the experimental data calculated from the electrochemical studies. The chromophore TPA1 exhibits solvatochromism and aggregation-induced emission (AIE) behavior owing to the emission in the solid state.

Common Inflammatory Markers and Outcome After Pediatric Cardiac Surgery With High Thoracic Epidural Anesthesia: A Randomized Controlled Study.

Background: High thoracic epidural analgesia (HTEA) plays a pivotal role in reducing stress and neuroendocrine response in cardiac surgeries. Aim: The primary objective is to assess the effect of HTEA, in pediatric cardiac surgery, on inflammatory markers (interleukin [IL]-6, IL-8, and tumor necrosis factor-α). The secondary objectives are to assess its effect on various organ systems, that is, pulmonary (PaO2, P/F ratio), renal (Creatinine clearance, somatic near infrared spectroscopy [NIRS], serum neutrophil gelatinase-associated lipocalin values), cardiac (cardiac index, serum Trop-I, and lactate levels), mechanical ventilation duration, and length of stay in hospital (LOS). Methods: The study included 188 pediatric patients, who underwent, on-pump cardiac surgery randomized into the Epidural Group (n = 92) and Non-Epidural Group (n = 96). After general anesthesia, a 23 G epidural catheter was placed at the T4-5 level with a Bupivacaine infusion while the Non-epidural Group received fentanyl infusion. Blood samples were collected at four-time points, T0(preop), T1(4 h), and on the first and second postoperative days (T2 and T3). Results: The inflammatory markers were reduced, while the outcomes variables of mechanical ventilation (MV) duration had lower values in the epidural group (19.5 h vs 47.3 h, P = .002). LOS was shorter (10.1 days vs 13.3 days, P = .016). pO2, PF ratio, and renal NIRS values were better in the Epidural Gp, while other parameters were comparable. Non-epidural Gp had more complications esp. Acute kidney injury requires RRT. Conclusion: HTEA use in pediatric, on-pump cardiac surgery offers a favorable profile in terms of reduction in the inflammatory markers and positive effect on the organ systems with lesser MV duration and the LOS.

Ca2+ Homeostasis by Plasma Membrane Ca2+ ATPase (PMCA) 1 Is Essential for the Development of DP Thymocytes.

The strength of Ca2+ signaling is a hallmark of T cell activation, yet the role of Ca2+ homeostasis in developing T cells before expressing a mature T cell receptor is poorly understood. We aimed to unveil specific functions of the two plasma membrane Ca2+ ATPases expressed in T cells, PMCA1 and PMCA4. On a transcriptional and protein level we found that PMCA4 was expressed at low levels in CD4-CD8- double negative (DN) thymocytes and was even downregulated in subsequent stages while PMCA1 was present throughout development and upregulated in CD4+CD8+ double positive (DP) thymocytes. Mice with a targeted deletion of Pmca1 in DN3 thymocytes had an almost complete block of DP thymocyte development with an accumulation of DN4 thymocytes but severely reduced numbers of CD8+ immature single positive (ISP) thymocytes. The DN4 thymocytes of these mice showed strongly elevated basal cytosolic Ca2+ levels and a pre-mature CD5 expression, but in contrast to the DP thymocytes they were only mildly prone to apoptosis. Surprisingly, mice with a germline deletion of Pmca4 did not show any signs of altered progression through the developmental thymocyte stages, nor altered Ca2+ homeostasis throughout this process. PMCA1 is, therefore, non-redundant in keeping cellular Ca2+ levels low in the early thymocyte development required for the DN to DP transition.

Comparative evaluation of high-flow nasal cannula oxygenation vs nasal intermittent ventilation in postoperative paediatric patients operated for acyanotic congenital cardiac defects.

Background: This study aimed to compare high-flow nasal cannula (HFNC) oxygenation vs nasal intermittent ventilation (NIV) oxygenation for respiratory care after extubation in postoperative paediatric cardiac patients. Methods: This study was a randomised controlled trial. One hundred twenty-one paediatric patients with acyanotic congenital heart disease undergoing corrective cardiac surgery on cardiopulmonary bypass were included in the study. Patients were randomised to receive either HFNC (AIRVO) or NIV (RAM Cannula) postextubation. Arterial blood gas was analysed at different time points perioperatively. Results: Patients in both the groups were matched with respect to diagnosis and demographic profiles. Baseline hemodynamic and respiratory parameters were also similar in both the groups. Patients in HFNC/AIRVO group did not show improved carbon dioxide (CO2) washout but showed improved pO2 and pO2/FiO2 ratio immediate postextubation. Reintubation rate and other intensive care unit (ICU) complications were similar in both the groups. Conclusion: Postcardiopulmonary bypass respiratory complications in paediatric patients with congenital acyanotic heart disease can be minimised with newer oxygen therapy devices such as AIRVO (HFNC) or RAM cannula (NIV). In comparison between these two, AIRVO did not show improved CO2 washout over RAM cannula; however, it did provide better oxygenation as measured by pO2 in arterial blood and pO2/FiO2 ratio immediate postextubation. Also, long-term results such as duration of mechanical ventilation and ICU stay were not affected by the choice of device.

Management of bronchomalacia in infants post-cardiac surgery using synchronized nasal DuoPAP: A novel technology.

Background: Tracheo-bronchomalacia (TBM) is the weakness in the structural integrity of the cartilaginous ring and arch. It may occur in isolation with prematurity or secondarily in association with various congenital anomalies. Bronchomalacia is more commonly associated with congenital heart diseases. The conventional treatment options include positive pressure ventilation with or without tracheostomy, surgical correction of external compression and airway stenting. Aim: To use "synchronized" nasal Dual positive airway pressure (DuoPAP), a non-invasive mode of ventilation as an alternative treatment option for bronchomalacia to avoid complications associated with conventional treatment modalities. Study Design: Prospective observational study conducted in Army Hospital Research and Referral from Jul 2019 to Dec 2020. Material and Methods: We diagnosed seven cases of TBM post-cardiac surgery at our institute, incidence of 4.2%. Four infants were diagnosed with left sided bronchomalacia, 2 were diagnosed with right sided bronchomalacia and one with tracheomalacia. Those infants were managed by "synchronized" nasal DuoPAP, a first in ventilation technology by Fabian Therapy Evolution ventilator (Acutronic, Switzerland). Results: All seven infants showed significant improvement with synchronized nasal DuoPAP both clinically as well as radiologically. None of the infant required tracheostomy and discharged to home successfully. Conclusion: The synchronized nasal DuoPAP is a low cost and effective treatment option for infants with TBM. It could be attributed to synchronization of the breaths leading to better tolerance and compliance in paediatric age group.

Fast-tracking with continuous thoracic epidural analgesia in paediatric congenital heart surgeries: an institutional experience.

Objective: To assess the success of fast-tracking in infants and small children undergoing paediatric cardiac surgery under general anaesthesia with continuous thoracic epidural analgesia (TEA). Methodology: It is a retrospective study at a tertiary care hospital. A total of 461 children, aged 12 years or younger, were operated for congenital heart disease over a 2-year period from January 2018 to December 2019. After the exclusion of 71 patients, data from the remaining 390 patients were analysed. Measurements and main results: The median time for extubation after intensive care unit admission was 2 h and 25 min (0-20 h). Extubation within 6 h was achieved in 215 patients (~ 55%). Patients in the early extubation group had significantly shorter hospital stay (4.1 ± 2.3 vs 6.9 ± 3.9 days, p = 0.004) than patients in the ventilated group. Reintubation was required in 27 (6.9%) patients. Thirteen patients died postoperatively on ventilator. Patients with low nadir temperature intraoperatively and cardiopulmonary bypass time > 90 min significantly predicted failure in fast-tracking with an odds ratio (OR) = 1.27; CI: 1.18-1.38 and OR = 2.3; CI: 1.8-2.96 respectively. The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery mortality score, younger age, Down syndrome and high vasopressor inotropic score did not adversely affect early extubation, contrary to contemporary concerns. Conclusions: A multimodal approach for perioperative pain relief and sedation consisting of propofol and dexmedetomidine infusion along with TEA ensures early extubation in 59% of the cases undergoing paediatric cardiac surgery. Our data suggests that fast-tracking is feasible with safe and superior outcomes in a subset of appropriate patients undergoing paediatric cardiac surgery. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-022-01373-8.

Ratio of Hydrophobic-Hydrophilic and Positive-Negative Residues at Lipid-Water-Interface Influences Surface Expression and Channel Gating of TRPV1.

During evolution, TRPV1 has lost, retained or selected certain residues at Lipid-Water-Interface (LWI) and formed specific patterns there. The ratio of "hydrophobic-hydrophilic" and "positive-negative-charged" residues at the inner LWI remains conserved throughout vertebrate evolution and plays important role in regulating TRPV1 trafficking and localization. Arg575 is an important residue as Arg575Asp mutant has reduced surface expression, co-localization with lipid raft markers, cell area and increased cell lethality. This lethality is most likely due to the disruption of the ratio between positive-negative charges caused by the mutation. Such lethality can be rescued by either using TRPV1-specfic inhibitor 5'-IRTX or by restoring the positive-negative charge ratio at that position, i.e. by introducing Asp576Arg mutation in Arg575Asp backbone. We propose that Arg575Asp mutation confers TRPV1 in a "constitutive-open-like" condition. These findings have broader implication in understanding the molecular evolution of thermo-sensitive ion channels and the micro-environments involved in processes that goes erratic in different diseases. The segment of TRPV1 that is present at the inner lipid-water-interface (LWI) has a specific pattern of amino acid combinations. The overall ratio of +ve charge /-ve charge and the ratio of hydrophobicity/hydrophilicity remain constant throughout the vertebrate evolution (ca 450 million years). This specific pattern is not observed in the outer LWI region of TRPV1.

Hydrogel-Mediated Release of TRPV1 Modulators to Fine Tune Osteoclastogenesis.

Bone defects, including bone loss due to increased osteoclast activity, have become a global health-related issue. Osteoclasts attach to the bone matrix and resorb the same, playing a vital role in bone remodeling. Ca2+ homeostasis plays a pivotal role in the differentiation and maturation of osteoclasts. In this work, we examined the role of TRPV1, a nonselective cation channel, in osteoclast function and differentiation. We demonstrate that endogenous TRPV1 is functional and causes Ca2+ influx upon activation with pharmacological activators [resiniferatoxin (RTX) and capsaicin] at nanomolar concentration, which enhances the generation of osteoclasts, whereas the TRPV1 inhibitor (5'-IRTX) reduces osteoclast differentiation. Activation of TRPV1 upregulates tartrate-resistant acid phosphatase activity and the expression of cathepsin K and calcitonin receptor genes, whereas TRPV1 inhibition reverses this effect. The slow release of capsaicin or RTX at a nanomolar concentration from a polysaccharide-based hydrogel enhances bone marrow macrophage (BMM) differentiation into osteoclasts whereas release of 5'-IRTX, an inhibitor of TRPV1, prevents macrophage fusion and osteoclast formation. We also characterize several subcellular parameters, including reactive oxygen (ROS) and nitrogen (RNS) species in the cytosol, mitochondrial, and lysosomal profiles in BMMs. ROS were found to be unaltered upon TRPV1 modulation. NO, however, had elevated levels upon RTX-mediated TRPV1 activation. Capsaicin altered mitochondrial membrane potential (ΔΨm) of BMMs but not 5'-IRTX. Channel modulation had no significant impact on cytosolic pH but significantly altered the pH of lysosomes, making these organelles less acidic. Since BMMs are precursors for osteoclasts, our findings of the cellular physiology of these cells may have broad implications in understanding the role of thermosensitive ion channels in bone formation and functions, and the TRPV1 modulator-releasing hydrogel may have application in bone tissue engineering and other biomedical sectors.

The role of three-dimensional printed cardiac models in the management of complex congenital heart diseases.

BACKGROUND: Three-dimensional printing is a process enabling computer-assisted conversion of imaging data from patients into physical "printed" replicas. This has been extrapolated to reconstructing patient-specific cardiac models in congenital heart diseases. The aim of this study was to analyze the impact of three-dimensional printing in surgical decision making in selected cases of complex congenital heart disease by creating patient-specific printed models. METHODS: Patients with complex congenital heart diseases with unresolved management decisions after evaluation by echocardiography, cardiac catheterization, and cardiac computed tomography were included with intent to aid in surgical decision making. Three-dimensional models were created from computed tomographic images by an outsourced firm using computer applications. All cases were reviewed by the same team before and after the cardiac models were prepared. The management decisions were grouped as either "corrective surgery" or "no surgery or palliation" The impact of the surgical decision pre and post three-dimensional cardiac model was analyzed by applying Cohen's kappa test of agreement. RESULTS: Ten patients were included, of which five were of increased pulmonary blood flow, and five were of decreased pulmonary flow. The commonest indication for three-dimensional printed models was to establish the routability of the aorta and pulmonary artery to their respective ventricles (in five patients). The nonagreement between the decision taken before and after the cardiac model was 80%, with kappa -0.37 and P value 0.98. CONCLUSIONS: Three-dimensional printed cardiac models contribute to better decision making in complex congenital heart diseases enabling safer execution of any complex congenital heart surgery.

A prospective randomized clinical study of perioperative oral thyroid hormone treatment for children undergoing surgery for congenital heart diseases.

CONTEXT: Thyroid hormone deficiency is known to occur after cardiac surgery and known as nonthyroid illness (NTI). The beneficial role of perioperative thyroid hormone supplementation in children has been debatable more so with oral supplementation. AIMS: The aim is to evaluate the role of pre-operative oral thyroid hormone therapy in preventing NTI. To assess its effect on post-operative thyroid hormone levels, hemodynamic parameters, and cardiac function of infants and small children undergoing pediatric cardiac surgery. SETTINGS AND DESIGN: Prospective randomized, double-blinded controlled trial at a tertiary level pediatric cardiothoracic center. MATERIALS AND METHODS: Sixty-five children aged under 18 months undergoing corrective surgeries on cardiopulmonary bypass were included. Patients were randomized into two equal groups: placebo group (given placebo) and thyroxine group (given thyroxine tablet 10 µg/kg) orally once a day starting on the preoperative evening till the fifth postoperative day. The postoperative hemodynamics, inotropic requirement, ventilatory requirement, and cardiac function on echocardiography were observed. STATISTICAL TESTS: Shapiro-Wilk test, Mann-Whitney/t-test, Chi-square test, ANOVA with Tukey correction were used. RESULTS: Serum triiodothyronine and thyroxine levels postoperatively were significantly higher in the thyroxine group than in the placebo group. There was no significant difference in left ventricular ejection fraction, hemodynamic variables, extubation time, and length of intensive care unit (ICU) stay between the two groups. CONCLUSIONS: In infants and small children undergoing corrective cardiac surgery, perioperative oral thyroid hormone therapy reduces the severity of postoperative NTI. It increases the serum level of thyroid hormones but the therapy does not translate to better hemodynamics, reduced inotropic requirement, reduced ventilatory requirement, improved myocardial function or reduced ICU stay when compared to placebo.

TRPM8 channel inhibitor-encapsulated hydrogel as a tunable surface for bone tissue engineering.

A major limitation in the bio-medical sector is the availability of materials suitable for bone tissue engineering using stem cells and methodology converting the stochastic biological events towards definitive as well as efficient bio-mineralization. We show that osteoblasts and Bone Marrow-derived Mesenchymal Stem Cell Pools (BM-MSCP) express TRPM8, a Ca2+-ion channel critical for bone-mineralization. TRPM8 inhibition triggers up-regulation of key osteogenesis factors; and increases mineralization by osteoblasts. We utilized CMT:HEMA, a carbohydrate polymer-based hydrogel that has nanofiber-like structure suitable for optimum delivery of TRPM8-specific activators or inhibitors. This hydrogel is ideal for proper adhesion, growth, and differentiation of osteoblast cell lines, primary osteoblasts, and BM-MSCP. CMT:HEMA coated with AMTB (TRPM8 inhibitor) induces differentiation of BM-MSCP into osteoblasts and subsequent mineralization in a dose-dependent manner. Prolonged and optimum inhibition of TRPM8 by AMTB released from the gels results in upregulation of osteogenic markers. We propose that AMTB-coated CMT:HEMA can be used as a tunable surface for bone tissue engineering. These findings may have broad implications in different bio-medical sectors.

TLR9 Polymorphisms Might Contribute to the Ethnicity Bias for EBV-Infected Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world, but is endemic in some ethnic groups. The association of NPC with the Epstein-Barr virus (EBV) is firmly established; however, the mechanism is still unclear. TLR9 is well known for its essential role in viral pathogen recognition and activation of innate immunity. Here, we report a set of TLR9 polymorphisms in the TIR-2 domain of the TLR9 protein collected from the EBV-infected NPC samples from northeast Indian populations sharing the aforesaid ethnicity. The occurrence of mutations is significantly high in these samples as we found a p value of <0.0001 at a significance level of 0.05. These might play an important role for the lack of function of TLR9 and thus for the higher occurrence of EBV-mediated NPC in such ethnic groups.