The Safety of the Laryngeal Mask Airway in Adenotonsillectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Adenotonsillectomy is one of the most common surgical procedures worldwide. The current standard for securing the airway in patients undergoing adenotonsillectomy is endotracheal tube (ETT) intubation. Several studies have investigated the use of the laryngeal mask airway (LMA) in this procedure. We conducted a systematic review and meta-analysis to compare the safety and efficacy of the LMA versus ETT in adenotonsillectomy. METHOD: Databases were searched from inception to 2022 for randomized controlled trials and comparative studies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The primary outcome is the rate of perioperative respiratory adverse events (PRAEs). Secondary outcomes included the rate of conversion to ETT, desaturations, nausea/vomiting, and surgical time. A subgroup analysis, risk of bias, publication bias, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessments were also performed. RESULTS: Twelve studies were included in the analysis (4176 patients). The mean overall conversion to ETT was 8.36% [95% confidence interval (CI) = 8.17, 8.54], and for the pediatric group 8.27% (95% CI = 8.08, 8.47). The mean rate of conversion to ETT secondary to complications was 2.89% (95% CI = 2.76, 3.03) while the rest was from poor surgical access. Overall, there was no significant difference in PRAEs [odds ratio (OR) 1.16, 95% CI = 0.60, 2.22], desaturations (OR 0.79, 95% CI = 0.38, 1.64), or minor complications (OR 0.89, 95% CI = 0.50, 1.55). The use of LMA yielded significantly shorter operative time (mean difference -4.38 minutes, 95% CI = -8.28, -0.49) and emergence time (mean difference -4.15 minutes, 95% CI = -5.63, -2.67). CONCLUSION: For adenotonsillectomy surgery, LMA is a safe alternative to ETT and requires less operative time. Careful patient selection and judgment of the surgeon and anesthesiologist are necessary, especially given the 8% conversion to ETT rate.

Evaluating the Association Between Iron Deficiency Anemia and Febrile Convulsion Among Children Aged 6-60 Months Admitted to a Tertiary Care Hospital in Eastern India: A Case-Control Study.

Background and objective Anemia, particularly iron deficiency anemia (IDA), presents a significant global health challenge, particularly among children under the age of five years in developing nations. Concurrently, febrile convulsions (FC) affect up to 5% of neurologically healthy children aged 6-60 months, causing considerable distress among parents. There is a suggested correlation between fever and iron deficiency, which may exacerbate neurological risks, potentially lowering seizure thresholds and increasing the risk of FC. However, studies investigating the relationship between IDA and FC have shown conflicting results. In light of this, this study aimed to explore this relationship among children aged 6-60 months in Eastern India, an area where this association has yet to be thoroughly investigated. Materials and methods The case-control study included children aged 6-60 months. The cases consisted of children presenting with FC, while controls comprised children in the same age group presenting with febrile illness but without seizures. Informed consent was obtained, a detailed history was taken, and clinical examinations were conducted for both groups. Blood investigations were performed to diagnose IDA according to WHO criteria: hemoglobin <11 gm/dl with the classical triad of low mean corpuscular volume (MCV), low mean corpuscular hemoglobin (MCH), and low mean corpuscular hemoglobin concentration (MCHC) for age. Data analysis was performed using the R-based software Jamovi 2.4.8. with appropriate statistical tests. Results We included 81 cases and 80 controls. The study found a statistically significant association between IDA and FC with an odds ratio (OR) of 2.25 [95% confidence interval (CI): 1.03-4.91; p=0.039]. Additionally, the study revealed that hemoglobin levels, MCH, MCV, and MCHC were lower among cases compared to controls, while the red cell distribution width (RDW) was higher. Both these findings regarding RBC indices were statistically significant (p<0.05). Conclusions Our findings indicate a statistically significant association between IDA and FC among children under five years of age. Implementing measures to prevent IDA and strengthening existing strategies may help alleviate the burden of FC in this vulnerable population.

Engineered vitamin E-tethered non-immunogenic facial lipopeptide for developing improved siRNA based combination therapy against metastatic breast cancer.

RNA interference based therapeutic gene silencing is an emerging platform for managing highly metastatic breast cancer. Cytosolic delivery of functional siRNA remains the key obstacle for efficient RNAi therapy. To overcome the challenges of siRNA delivery, we have engineered a vitamin E-tethered, short, optimum protease stabilized facial lipopeptide based non-immunogenic, biocompatible siRNA transporter to facilitate the clinical translation in future. Our designed lipopeptide has an Arginine-Sarcosine-Arginine segment for providing optimum protease-stability, minimizing adjacent arginine-arginine repulsion and reducing intermolecular aggregation and α-tocopherol as the lipidic moiety for facilitating cellular permeabilization. Interestingly, our designed non-immunogenic siRNA transporter has exhibited significantly better long term transfection efficiency than HiPerFect and can transfect hard to transfect primary cell line, HUVEC. Our engineered siRNA therapeutics demonstrated high efficacy in managing metastasis against triple negative breast cancer by disrupting the crosstalk of endothelial cells and MDA-MB-231 and reduced stemness and metastatic markers, as evidenced by downregulating critical oncogenic pathways. Our study aimed at silencing Notch1 signalling to achieve "multi-targeted" therapy with a single putative molecular medicine. We have further developed mechanistically rational combination therapy combining Notch1 silencing with a repurposed drug m-TOR inhibitor, metformin, which demonstrated synergistic interaction and enhanced antitumor efficacy against cancer metastasis.

Harnessing Peptide-Functionalized Multivalent Gold Nanorods for Promoting Enhanced Gene Silencing and Managing Breast Cancer Metastasis.

Small interfering RNA (siRNA) has become the cornerstone against undruggable targets and for managing metastatic breast cancer. However, an effective gene silencing approach is faced with a major challenge due to the delivery problem. In our present study, we have demonstrated efficient siRNA delivery, superior gene silencing, and inhibition of metastasis in triple-negative breast cancer cells (MDA-MB-231) using rod-shaped (aspect ratio: 4) multivalent peptide-functionalized gold nanoparticles and compared them to monovalent free peptide doses. Multivalency is a new concept in biology, and tuning the physical parameters of multivalent nanoparticles can enhance gene silencing and antitumor efficacy. We explored the effect of the multivalency of shape- and size-dependent peptide-functionalized gold nanoparticles in siRNA delivery. Our study demonstrates that peptide functionalization leads to reduced toxicity of the nanoparticles. Such designed peptide-functionalized nanorods also demonstrate antimetastatic efficacy in Notch1-silenced cells by preventing EMT progression in vitro. We have shown siRNA delivery in the hard-to-transfect primary cell line HUVEC and also demonstrated that the Notch1-silenced MDA-MB-231 cell line has failed to form nanobridge-mediated foci with the HUVEC in the co-culture of HUVEC and MDA-MB-231, which promote metastasis. This antimetastatic effect is further checked in a xenotransplant in vivo zebrafish model. In vivo studies also suggest that our designed nanoparticles mediated inhibition of micrometastasis due to silencing of the Notch1 gene. The outcome of our study highlights that the structure-activity relationship of multifunctional nanoparticles can be harnessed to modulate their biological activity.

Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson's model.

Parkinson's disease (PD) is a neuromotor disorder, primarily manifested by motor anomalies due to progressive loss of dopaminergic neurons. Although alterations in genetic factors have been linked with its etiology, exponential accumulation of environmental entities such as reactive oxygen species (ROS) initiate a cyclic chain reaction resulting in accumulation of cellular inclusions, dysfunctional mitochondria, and overwhelming of antioxidant machinery, thus accelerating disease pathogenesis. Involvement of oxidative stress in PD is further substantiated through ROS induced Parkinsonian models and elevated oxidative markers in clinical PD samples; thereby, making modulation of neuronal oxidative load as one of the major approaches in management of PD. Here we have found a potent antioxidant moiety Scopoletin (Sp), a common derivative in most of the nootropic herbs, with robust neuroprotective ability. Sp increased cellular resistance to ROS through efficient recycling of GSH to prevent oxidative damage. The Sp treated cells showed higher loads of reduced glutathione making them resistant to perturbation of antioxidant machinery or neurotoxin MPP+. Sp could restore the redox balance, mitochondrial function, and prevented oxidative damage, leading to recovery of dopaminergic neural networks and motion abilities in Drosophila genetic model of PD. Our data also suggest that Sp, in combination increases the therapeutic potency of L-DOPA by mitigating its chronic toxicity. Together, we highlight the possible ability of Sp in preventing oxidative stress mediated loss of dopaminergic neurons and at the same time enhance the efficacy of dopamine recharging regimens.

Engineered Histidine-Enriched Facial Lipopeptides for Enhanced Intracellular Delivery of Functional siRNA to Triple Negative Breast Cancer Cells.

Cytosolic delivery of functional siRNA remains the major challenge to develop siRNA-based therapeutics. Designing clinically safe and effective siRNA transporter to deliver functional siRNA across the plasma and endosomal membrane remains a key hurdle. With the aim of improving endosomal release, we have designed cyclic and linear peptide-based transporters having an Arg-DHis-Arg template. Computational studies show that the Arg-DHis-Arg template is also stabilized by the Arg-His side-chain hydrogen bonding interaction at physiological pH, which dissociates at lower pH. The overall atomistic interactions were examined by molecular dynamics simulations, which indicate that the extent of peptide_siRNA assembly formation depends greatly on physicochemical properties of the peptides. Our designed peptides having the Arg-DHis-Arg template and two lipidic moieties facilitate high yield of intracellular delivery of siRNA. Additionally, unsaturated lipid, linoleic acid moieties were introduced to promote fusogenicity and facilitate endosomal release and cytosolic delivery. Interestingly, such protease-resistant peptides provide serum stability to siRNA and exhibit high efficacy of erk1 and erk2 gene silencing in the triple negative breast cancer (TNBC) cell line. The peptide having two linoleyl moieties demonstrated comparable efficacy with commercial transfection reagent HiPerFect, as evidenced by the erk1 and erk2 gene knockdown experiment. Additionally, our study shows that ERK1/2 silencing siRNA and doxorubicin-loaded gramicidin-mediated combination therapy is more effective than siRNA-mediated gene silencing-based monotherapy for TNBC treatment.

Use of Serratus Plane Block for Repair of Coarctation of Aorta: A Report of 3 Cases.

OBJECTIVES: The practice of regional anesthesia techniques (thoracic, epidural, paravertebral) in pediatric cardiac surgery enhances perioperative outcomes such as improved perioperative analgesia, decreased stress response, early extubation, and shortened hospital stay. However, these blocks can be technically challenging and can be associated with unacceptable failure rate and complications in infants. For these reasons, regional anesthesia is sometimes avoided in pediatric cardiac surgery. We describe the simple and effective serratus plane block for thoracotomy analgesia in 2 neonates and a child. CASE REPORT: We present 3 pediatric patients, each of whom was having coarctation repair and received an ultrasound-guided serratus plane block for thoracotomy analgesia. The patients were 3 days, 14 days, and 4 years old, weighing from 1.9 to 16 kg. The serratus plane block was performed prior to surgical incision. The block was technically simple compared with thoracic epidural or paravertebral block. All patients were extubated immediately after completion of surgery. Apart from the induction dose of fentanyl (2 µg/kg), no further opioids were required intraoperatively. Postoperative opioid requirements as well as duration of intensive care and hospital stay were lower than recent averages (for the same demographic and procedure) in our hospital. CONCLUSIONS: We propose that the serratus plane block is a simple procedure that provides good perioperative analgesia for infant thoracotomy, potentially facilitating early extubation and a shorter hospital stay.

Relative Contributions of Adductor Canal Block and Intrathecal Morphine to Analgesia and Functional Recovery After Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Effective postoperative analgesia may enhance early rehabilitation after orthopedic surgery. This randomized double-blind trial investigates the relative contributions of adductor canal block and low-dose intrathecal morphine (ITM) to postoperative analgesia and functional recovery after total knee arthroplasty. METHODS: Two-hundred one patients undergoing elective unilateral total knee arthroplasty under spinal anesthesia were randomized to 3 groups. All patients received standardized intraoperative local infiltration analgesia and postoperative oral analgesics. Patients in group 1 received a "sham" adductor canal block with 30 mL of normal saline. Patients in group 2 received an adductor canal block with 30 mL of ropivacaine 0.5% with 1:400,000 epinephrine, whereas patients in group 3 received the adductor canal block with the active drug and 100 µg of ITM. The primary outcome measure was the Timed Up and Go (TUG) test on the second postoperative day. Secondary outcomes included postoperative pain scores and opioid requirements, distance walked, time to hospital discharge, and self-reported functional outcomes at 3 months. RESULTS: All 3 groups had similar values of TUG test on postoperative day (POD) 2 (46 [36-62], 45 [33-61], and 52 [41-69]; P = 0.166) as well as other short-term and 3-month functional outcomes. Patients in group 3 showed a favorable analgesic profile as evidenced by 3 positive secondary outcomes. These positive outcomes were lower pain scores 12 hours postoperatively both at rest (4 [2-6.3], 4 [2.3-6], and 3 [1-4]; P = 0.007) and on movement (6 [4-8], 6 [3-8], and 4 [2-6]; P = 0.002), a lower incidence of "rescue" intravenous patient-controlled analgesia (42%, 34%, and 20%; P = 0.031), and the lowest cumulative opioid requirements for the first 48 hours postoperatively (86 ± 71, 68 ± 46, and 59 ± 39; P < 0.005, group 3 compared with group 1). CONCLUSIONS: Our data suggest that there is no difference in either the primary outcome of TUG test on POD 2, other immediate functional secondary outcomes, or in global functional outcome at 3 months postoperatively across all 3 groups. Our data also suggest an improved analgesic profile in the first 48 hours postoperatively when both adductor canal block and low-dose ITM (100 µg) are added to local infiltration analgesia as evidenced by several positive secondary outcomes of lower pain scores and opioid requirements. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, identifier NCT02411149.

Applications of surface-enhanced Raman scattering in advanced bio-medical technologies and diagnostics.

In this review of the literature on surface-enhanced Raman scattering (SERS), we describe recent developments of this technique in the medical field. SERS has developed rapidly in the last few years as a result of the fascinating advancements in instrumentation and the ability to interpret complex Raman data using high-processional, computer-aided programs. This technique, has many advantages over ordinary spectroscopic analytical techniques - such as extremely high sensitivity, molecular selectivity, intense signal and great precision - that can be leveraged to address complex medical diagnostics problems. This review focuses on the SERS-active substrate, as well as major advances in cancer and bacteria detection and imaging. Finally, we present a perspective on anticipated future advancements in SERS techniques to address some of the most critical challenges in the areas of diagnostics, detection, and sensing.

Bionanomaterials for bone tumor engineering and tumor destruction.

Recent advances have led to the development of multifunctional bionanomaterials that can target a bone tumor and deliver therapeutic drugs or genes. Bionanomaterial-based bone cancer treatment offers hope for treating bone cancer and provides many exciting possibilities to enable important new therapeutic outcomes. Physicists, chemists, engineers, biologists, and clinicians will continue to address research questions at the level of fundamental biology and science to develop novel biomaterials and systems, particularly enabling cost-effective and large-scale production of multifunctional nanomaterial systems. This review provides a comprehensive reflection of the recent advancements in bionanomaterials for use in bone cancer treatment. The review examines in detail different bionanomaterials (hydroxyapatite nanocrystals and nanometals, nanoscale conjugated copolymer, selenium and liposome) that have been researched and developed over the last six years for bone tissue engineering. It also discusses an important area of research - the use of engineered bone scaffolds in cancer treatment. Recently, bone scaffolds have been identified as potential targets for metastatic spread as well as a means by which escape from tumor dormancy can be studied. This review also includes discussions of a highly potent new class of anticancer compounds, e.g., geminal bisphosphonates, that has been shown to have strong affinity towards various hydroxyapatite-based bone scaffolds with controlled adsorption and release for anticancer activity. Finally, perspectives on future directions in nanotechnology-enabled bone tumor treatment are presented.

Graphene oxide-based supramolecular hydrogels for making nanohybrid systems with Au nanoparticles.

In the presence of a small amount of a proteinous amino acid (arginine/tryptophan/histidine) or a nucleoside (adenosine/guanosine/cytidine), graphene oxide (GO) forms supramolecular stable hydrogels. These hydrogels have been characterized by field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), X-ray diffraction (XRD) analysis, Raman spectroscopy, and rheology. The morphology of the hydrogel reveals the presence of nanofibers and nanosheets. This suggests the supramolecular aggregation of GO in the presence of an amino acid/nucleoside. Rheological studies of arginine containing a GO-based hydrogel show a very high G' value (6.058 × 10(4) Pa), indicating the rigid, solid-like behavior of this gel. One of these hydrogels (GO-tryptophan) has been successfully utilized for the in situ synthesis and stabilization of Au nanoparticles (Au NPs) within the hydrogel matrix without the presence of any other external reducing and stabilizing agents to make Au NPs containing the GO-based nanohybrid material. The Au NPs containing the hybrid hydrogel has been characterized by using UV/vis spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM). In this study, gold salt (Au(3+)) has been bioreduced by the tryptophan within the hydrogel. This is a facile "green chemical" method of preparing the GO-based nanohybrid material within the hydrogel matrix. The significance of this method is the in situ reduction of gold salt within the gel phase, and this helps to decorate the nascently formed Au NPs almost homogeneously and uniformly on the surface of the GO nanosheets within the gel matrix.