Reconstruction of Midface Defects after Radical Tumor Resection - a Rare Case Report of Solitary Fibrous Tumour of the Hard Palate.

Introduction- Spindle cell neoplasm is a variant of squamous cell carcinoma. One of its subtypes is solitary fibrous tumor. Its occurrence in head and neck is very rare and rarer in hard palate. But if occurs, radical excision is the only choice as it has malignant potential but coverage of such large mid face defects imposes a challenge in front of a Plastic Surgeon as it demands both soft tissue coverage and skeletal support. Report of the case- A 33 year male presented to our department with swelling of left side face involving the anterior palate, maxilla, nose, and upper lip. With the help of the surgical oncology team, wide local excision of the neoplasm along with bilateral infrastructure maxillectomy, total rhinectomy, total upper lip resection and total hard palatectomy was done. This created large defect in the mid face which was covered with free anterolateral thigh flap. Biopsy was done which revealed the swelling as a solitary fibrous tumor of hard palate. All the margins were free of tumour. The flap settled well. Nostrils were secured with nasal stents. After 3 months, an expander was placed in forehead of the patient for future nasal reconstruction. After 3 months, nasal reconstruction was done using expanded forehead flap and costal cartilage. After 21 days flap detachment and insetting was done. White roll creation was also done. One more secondary procedure was done for flap thinning as patient had complain of nasal obstruction. After 6 months vascularised free fibula bone graft was introduced to reconstruct maxilla for future dental rehabilitation. The patient is in regular follow up and he is satisfied with the results. Discussion- Mid face defects involving perioral and nasomaxillar areas are very uncommon and require composite reconstruction. In such cases, microvascular free flap coverage is an irreplaceable option. Multiple stages might have to be done for further refinement. Conclusion- Reconstruction after oncological resection is always very demanding. With proper preoperative planning and skilled execution, the patient can be benefited functionally, aesthetically and psychosocially.

Association between baseline insulin resistance and hospital mortality in moderate-to-severe coronavirus disease 2019 patients without diabetes mellitus: An observational study.

Background: Insulin resistance is often implicated as a risk factor of cell-mediated immune dysfunction in sepsis patients and results in poor clinical outcome. However, it is unclear whether early insulin resistance is contributory to T-cell dysfunction and poor clinical outcome in coronavirus disease 2019 (COVID-19) patients. Methods: Adult patients with moderate-to-severe or critically ill COVID-19 infection were included in this study. Serum samples were collected at the time of diagnosis for fasting plasma glucose, serum insulin, serum cortisol, and serum glucagon measurements, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated. Results: One hundred and twenty-six subjects with a mean (standard deviation) age of 49.6 (16.3) years were recruited in this study, and 62.4% (78 of 125 patients) were male. HOMA-IR was a predictor of inhospital mortality with the area under the receiver operating characteristics curve (AUROC) (95% confidence interval [CI] of 0.61 [0.49-0.73]). With a cutoff value of 1.91, sensitivity was 75.5% and specificity was 45.2%. Higher serum insulin was associated with higher survival with AUROC (95% CI) of 0.65 (0.53-0.76), and the best cutoff was 7.15, with a sensitivity and specificity of 62.1% and 64.5%. Serum cortisol was also a predictor of inhospital mortality with an AUROC (95% CI) of 0.67 (0.56-0.77). Conclusion: An independent association between baseline serum cortisol and poor outcome in moderate-to-severe COVID-19 patients was observed. Hyperglycemia and HOMA-IR can also predict poor outcome in these patients with some accuracy.

A rare case of chikungunya encephalitis and its management: A case report and literature review.

Key Clinical Message: Chikungunya encephalitis, though rare, warrants clinical attention due to its severe complications. Early identification and appropriate management are crucial for improved outcomes in patients with this rare manifestation of chikungunya virus (CHIKV) infection. Abstract: CHIKV infection is commonly associated with fever and joint pains, but neurological complications such as encephalitis are rare. Here, we present a unique case of confirmed chikungunya encephalitis in a 12-year-old male exhibiting atypical neurological symptoms. The diagnostic journey involved comprehensive neuroimaging and serological investigations, revealing intriguing findings on magnetic resonance imaging and positive CHIKV RNA in serum and cerebrospinal fluid. We discuss the clinical presentation, radiological characteristics, and management strategies, emphasizing the importance of recognizing this uncommon neurological manifestation of CHIKV infection.

The unexpected fast polymerization during the synthesis of a glycolated polythiophene.

Conjugated polymers with ethylene glycol side chains are emerging as ideal materials for bioelectronics, particularly for application in organic electrochemical transistors (OECTs). To improve the OECT device performance, it is important to develop an efficient synthetic strategy that will provide access to novel high-performing materials besides focusing on molecular design. While a lot of efforts are being devoted to designing of new polymers by modifying the glycol side chains, understanding how their nature affects the polymerization kinetics and eventually the polymer structure and properties is not known. In this work, we have studied the influence of the content of the ethylene glycol side chain and its linkage on the formation of the active Grignard monomer species upon Grignard metathesis in three thiophene derivatives. A strong dependence of the monomer's concentration on polymerization was noted in our study indicating that for synthesizing P3MEEMT, a high-performing OECT material, by Kumada catalyst transfer polymerization (KCTP) a minimum of 0.15 M monomer is needed. Furthermore, kinetic studies by GPC show uncontrolled polymerization behavior contrary to the controlled chain growth characteristics of the KCTP.

High Rate, Dendrite Free Lithium Metal Batteries of Extended Cyclability via a Scalable Separator Modification Approach.

Owing to their great promise of high energy density, the development of safer lithium metal batteries (LMBs) has become the necessity of the hour. Herein, a scalable method based on conventional Celgard membrane (CM) separator modification is adopted to develop high-rate (10 mA cm-2 ) dendrite-free LMBs of extended cyclability (>1000 hours, >1500 cycles with 3 mA cm-2 , the bare fails within 50 cycles) with low over potential losses. The CM modification method entails the deposition of thin coatings of (≈6.6 µm) graphitic fluorocarbon (FG) via a large area electrophoretic deposition, where it helps for the formation of a stable LiF and carbon rich solid electrolyte interface (SEI) aiding a uniform lithium deposition even in higher fluxes. The FG@CM delivers a high transport number for Li ion (0.74) in comparison to the bare CM (0.31), indicating a facile Li ion transport through the membrane. A mechanistic insight into the role of artificial SEI formation with such membrane modification is provided here with a series of electrochemical as well as spectroscopic in situ/ex situ and postmortem analyses. The simplicity and scalability of the technique make this approach unique among other reported ones towards the advancement of safer LMBs of high energy and power density.

Validating the Performance of Modified Early Obstetrics Warning Score (MEOWS) for Prediction of Obstetrics Morbidity: A Prospective Observational Study in a Tertiary Care Institute in East India.

Background: An early warning score can be used to identify worsening in obstetric patients as they are more prone for deterioration. This study was conducted to evaluate and validate the performance of the modified early obstetric warning system (MEOWS) as a screening tool for early prediction of severe obstetric morbidity. Methods: This prospective observational study was conducted at obstetrics and gynaecology department, Tata Main Hospital, Jamshedpur, Jharkhand, India. A total of 1800 patients were included over a period of 10 month, from December 2021 to September 2022. Study population included all pregnant women admitted in labour room with > 28 weeks of gestation till 6 weeks postpartum. MEOWS charts were plotted for each patient, score calculated and documented at admission. Patients were categorized based on this score for further management, and follow-up was made till discharge. Outcome assessment was done in terms of ICU admission, length of hospital stays, obstetric morbidity, and maternal mortality. Correlation of each outcome with scoring was evaluated. Results: The sensitivity of MEOWS in predicting maternal morbidity was 72.91%, specificity 91.87%, positive predictive value 85.96%, and negative predictive value 83.24%. The area under receiver operator characteristic of MEOWS for prediction of maternal mortality was 0.79 (95% CI 0.75-0.82). Conclusion: MEOWS helps in early recognition of obstetric morbidity even before signs, and symptoms become clinically evident. It is a useful tool for predicting adverse maternal outcome in pregnant women.

Unveiling Potential Targeted Therapeutic Opportunities for Co-Overexpressed Targeting Protein for Xklp2 and Aurora-A Kinase in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most prevalent and leading causes of cancer deaths globally, with limited diagnostic and clinically significant therapeutic targets. Identifying the genes and processes involved in developing and progressing LUAD is crucial for developing effective targeted therapeutics and improving patient outcomes. Therefore, the study aimed to explore the RNA sequencing data of LUAD from The Cancer Genome Atlas (TCGA) and gene expression profile datasets involving GSE10072, GSE31210, and GSE32863 from the Gene Expression Omnibus (GEO) databases. The differential gene expression and the downstream analysis determined clinically significant biomarkers using a network-based approach. These therapeutic targets predominantly enriched the dysregulation of mitotic cell cycle regulation and revealed the co-overexpression of Aurora-A Kinase (AURKA) and Targeting Protein for Xklp2 (TPX2) with high survival risk in LUAD patients. The hydrophobic residues of the AURKA-TPX2 interaction were considered as the target site to block the autophosphorylation of AURKA during the mitotic cell cycle. The tyrosine kinase inhibitor (TKI) dacomitinib demonstrated the strong binding potential to hinder TPX2, shielding the AURKA destabilization. This in silico study lays the foundation for repurposing targeted therapeutic options to impede the Protein-Protein Interactions (PPIs) in LUAD progression and aid in future translational investigations.

Bioengineered Ciprofloxacin-Loaded Chitosan Nanoparticles for the Treatment of Bovine Mastitis.

Mastitis is the most devastating economic disease in dairy cattle. Mastitis in dairy cattle frequently occurs during the dry period or during early lactation. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus)are the main causative agents of mastitis in India. S. aureus can form microabscesses in the udder and develop a subclinical form of mastitis. This bacterial property hinders an effective cure during the lactation period. Antimicrobials used for treatments have a short half-life at the site of action because of frequent milking; thereforethey are unable to maintain the desired drug concentration for effective clearance of bacteria. We demonstrated the potential of ciprofloxacin-encapsulated nanocarriersthat can improve the availability of drugs and provide an effective means for mastitis treatment. These drug-loaded nanoparticles show low toxicity and slow clearance from the site of action. Antimicrobial activity against clinical strains of E. coli and S. aureus showed that the zone of inhibition depended on the dose (0.5 mg to 2 mg/mL nanoparticle solution from 11.6 to 14.5 mm and 15 to 18 mm). These nanoparticles showed good antimicrobial activity in broth culture and agar diffusion assay against bacteria.

Corrigendum: Triglyceride-mimetic prodrugs of buprenorphine enhance oral bioavailability via promotion of lymphatic transport.

[This corrects the article DOI: 10.3389/fphar.2022.879660.].

Macrophage Cx43 Is Necessary for Fibroblast Cytosolic Calcium and Lung Fibrosis After Injury.

Macrophages are paracrine signalers that regulate tissular responses to injury through interactions with parenchymal cells. Connexin hemichannels have recently been shown to mediate efflux of ATP by macrophages, with resulting cytosolic calcium responses in adjacent cells. Here we report that lung macrophages with deletion of connexin 43 (MacΔCx43) had decreased ATP efflux into the extracellular space and induced a decreased cytosolic calcium response in co-cultured fibroblasts compared to WT macrophages. Furthermore, MacΔCx43 mice had decreased lung fibrosis after bleomycin-induced injury. Interrogating single cell data for human and mouse, we found that P2rx4 was the most highly expressed ATP receptor and calcium channel in lung fibroblasts and that its expression was increased in the setting of fibrosis. Fibroblast-specific deletion of P2rx4 in mice decreased lung fibrosis and collagen expression in lung fibroblasts in the bleomycin model. Taken together, these studies reveal a Cx43-dependent profibrotic effect of lung macrophages and support development of fibroblast P2rx4 as a therapeutic target for lung fibrosis.

Triglyceride-Mimetic Prodrugs of Buprenorphine Enhance Oral Bioavailability via Promotion of Lymphatic Transport.

Buprenorphine (BUP) is a potent opioid analgesic that is widely used for severe pain management and opioid replacement therapy. The oral bioavailability of BUP, however, is significantly limited by first-pass metabolism. Previous studies have shown that triglyceride (TG) mimetic prodrugs of the steroid hormone testosterone circumvent first-pass metabolism by directing drug transport through the intestinal lymphatics, bypassing the liver. The current study expanded this prodrug strategy to BUP. Here different self-immolative (SI) linkers were evaluated to conjugate BUP to the 2 position of the TG backbone via the phenol group on BUP. The SI linkers were designed to promote drug release in plasma. Lipolysis of the prodrug in the intestinal tract was examined via incubation with simulated intestinal fluid (SIF), and potential for parent drug liberation in the systemic circulation was evaluated via incubation in rat plasma. Lymphatic transport and bioavailability studies were subsequently conducted in mesenteric lymph duct or carotid artery-cannulated rats, respectively. TG prodrug derivatives were efficiently transported into the lymphatics (up to 45% of the dose in anaesthetised rats, vs. less than 0.1% for BUP). Incorporation of the SI linkers facilitated BUP release from the prodrugs in the plasma and in concert with high lymphatic transport led to a marked enhancement in oral bioavailability (up to 22-fold) compared to BUP alone. These data suggest the potential to develop an orally bioavailable BUP product which may have advantages with respect to patient preference when compared to current sublingual, transdermal patch or parenteral formulations.

Circular Discovery in Small Molecule and Conjugated Polymer Synthetic Methodology.

Simple and efficient methods are a key consideration for small molecule and polymer syntheses. Direct arylation polymerization (DArP) is of increasing interest for preparing conjugated polymers as an effective approach compared to conventional cross-coupling polymerizations. As DArP sees broader utilization, advancements are needed to access materials with improved properties and different monomer structures and to improve the scalability of conjugated polymer synthesis. Presented herein are considerations for developing new methods of conjugated polymer synthesis from small molecule transformations, exploring how DArP has successfully used this approach, and presenting how emerging polymerization methodologies are developing similarly. While it is common to adapt small molecule methods to polymerizations, we demonstrate the ways in which information gained from studying polymerizations can inform and inspire greater advancements in small molecule transformations. This circular approach to organic synthetic method development underlines the value of collaboration between small molecule and polymer-based synthetic research groups.

Comparative evaluation of the analgesic efficacy of ultrasound-guided erector spinae plane block versus intrathecal morphine in patients undergoing percutaneous nephrolithotomy surgery: A prospective randomized pilot study.

OBJECTIVES: Existing research on erector spinae plane block and intrathecal morphine in patients undergoing percutaneous nephrolithotomy surgery is limited. METHODS: In this prospective, randomized study, 60 patients aged between 18 and 60 years were randomized into two groups (erector spinae plane block and intrathecal morphine). In the erector spinae plane block group, ultrasound-guided erector spinae plane block was performed, following which a mixture of 20 mL of 0.375% ropivacaine and 0.5 mcg/kg of clonidine was injected. In the intrathecal morphine group, 150 mcg preservative-free morphine with 2 mL of normal saline was administered intrathecally. The primary outcome was to evaluate the perioperative opioid consumption in the first 24 h. The secondary outcomes were to evaluate hemodynamic response to surgical stimulus, visual analogue scale score, time to first analgesic requirement, postoperative nausea and vomiting, postoperative opioid consumption, urethral irritation, and incidence of drug-related adverse effects. RESULTS: Total perioperative opioid consumption in the erector spinae plane block group was 355.0 (265.0, 485.0) µg and 240.0 (145.0, 370.0) µg in the intrathecal morphine group (P = 0.09). However, the patients in the erector spinae plane block group had significantly greater postoperative fentanyl consumption (235.0 [120.0, 345.0] µg) compared with those in the intrathecal morphine group (105.0 [30.0, 225.0] µg). There were no statistically significant differences noted for intraoperative opioid consumption, postoperative visual analogue scale score, time to first analgesic request, postoperative nausea and vomiting, and catheter irritation between the two groups. CONCLUSIONS: Although no statistically significant difference in intraoperative opioid consumption was seen between the erector spinae plane block and intrathecal morphine groups, postoperative opioid consumption was significantly higher in the erector spinae plane block group than in the intrathecal morphine group in patients undergoing percutaneous nephrolithotomy surgery.

Interaction with Patients as a Budding Doctor: An Experience.

Every medical student amidst COVID-19 missed out on an integral part of medical education which is interaction with patients as all the physical classes were postponed for months. Effective interaction with patients is the heart of medicine and it provides a synergistic effect on the delivery of high-quality care to the patient. However many medical students underestimate the art of communication. This article highlights the importance of basic communication skills; also encourages reflecting upon the whole experience and extracting the learning to apply to any further interactions. Keywords: communication; empathy; medical students; healthcare quality.

Indian goose berry fortified, anti-oxidant rich bael (Aegle marmelos) fermented beverage.

Bael (Aegle marmelos Correa), an important fruit of Indian subtropics, traditionally utilized in the preparation of preserve, candy, squash, RTS, etc. has immense therapeutic potential. An attempt was made to develop a bael based low alcoholic sweet fermented beverage ( may be called as bael cider), anti-oxidant fortified with 0.25 per cent bael leaf or 10 per cent Indian goose berry (Emblica officinalis Gaertn.) juice in separate batches. Unfortified bael pulp based drink was kept as control. The ameliorated pulp was fermented at 30 ± 2ºC using Saccharomyces cerevisiae. The gooseberry blended bael fermented beverage had higher anti-oxidant content in the form of phenolics (323 mg/100 ml) than leaf extract added fermented beverage (265 mg/100 ml) and control (266 mg/100 ml). Sensory evaluation of product revealed that gooseberry blended fermented beverage scored higher (8.2/10) than bael leaf blended fermented beverage (7.9/10) and control (7.0/10). Twelve months maturation study of beverage revealed increase in reducing sugars and decrease in phenolic content in all the treatments. Bael fermented beverage with gooseberry blend retained highest phenolic content (257 mg/100 ml) and sensory score 7.8/10. The study inferred that an acceptable quality fermented drink could be prepared from bael-gooseberry blend, which could be stored for one year with higher antioxidant value and minimum deterioration in the quality.

Modulating α-Synuclein Liquid-Liquid Phase Separation.

Liquid-liquid phase separation (LLPS) is a crucial phenomenon for the formation of functional membraneless organelles. However, LLPS is also responsible for protein aggregation in various neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease (PD). Recently, several reports, including ours, have shown that α-synuclein (α-Syn) undergoes LLPS and a subsequent liquid-to-solid phase transition, which leads to amyloid fibril formation. However, how the environmental (and experimental) parameters modulate the α-Syn LLPS remains elusive. Here, we show that in vitro α-Syn LLPS is strongly dependent on the presence of salts, which allows charge neutralization at both terminal segments of protein and therefore promotes hydrophobic interactions supportive for LLPS. Using various purification methods and experimental conditions, we showed, depending upon conditions, α-Syn undergoes either spontaneous (instantaneous) or delayed LLPS. Furthermore, we delineate that the kinetics of liquid droplet formation (i.e., the critical concentration and critical time) is relative and can be modulated by the salt/counterion concentration, pH, presence of surface, PD-associated multivalent cations, and N-terminal acetylation, which are all known to regulate α-Syn aggregation in vitro. Together, our observations suggest that α-Syn LLPS and subsequent liquid-to-solid phase transition could be pathological, which can be triggered only under disease-associated conditions (high critical concentration and/or conditions promoting α-Syn self-assembly). This study will significantly improve our understanding of the molecular mechanisms of α-Syn LLPS and the liquid-to-solid transition.

Central Placenta Previa With Coexisting Central Cervical Fibroid in Pregnancy: An Obstetrician's Nightmare.

Pregnancy with central placenta praevia and a coexistent cervical fibroid is infrequently encountered in clinical practice. A patient with this unusual combination is a nightmare for any clinician, especially if she presents with obstetric emergencies. In this scenario, there is a high chance of catastrophic obstetric hemorrhage during the peripartum period leading to a fatal outcome. We report a case of a 27-year-old lady at term pregnancy, who was brought to emergency in labor pain with antepartum hemorrhage. Subsequently, she was diagnosed to have central placenta praevia along with a large central cervical fibroid. An emergency cesarean section was performed to deliver the child. Intraoperatively, she had a major postpartum hemorrhage which was successfully managed with intrauterine balloon tamponade, hemostatic sutures, and uterine artery ligation. We could avoid cesarean hysterectomy by precise anticipation, meticulous planning, and step-wise protocol-driven management.

Selective Activation of MST1/2 Kinases by Retinoid Agonist Adapalene Abrogates AURKA-Regulated Septic Arthritis.

Septic arthritis is a chronic inflammatory disorder caused by Staphylococcus aureus invasion of host synovium, which often progresses to impairment of joint functions. Although it is known that disease progression is intricately dependent on dysregulated inflammation of the knee joint, identification of molecular events mediating such imbalance during S. aureus-induced septic arthritis still requires detailed investigation. In this article, we report that Aurora kinase A (AURKA) responsive WNT signaling activates S. aureus infection-triggered septic arthritis, which results in inflammation of the synovium. In this context, treatment with adapalene, a synthetic retinoid derivative, in a mouse model for septic arthritis shows significant reduction of proinflammatory mediators with a simultaneous decrease in bacterial burden and prevents cartilage loss. Mechanistically, adapalene treatment inhibits WNT signaling with concomitant activation of HIPPO signaling, generating alternatively activated macrophages. Collectively, we establish adapalene as a promising strategy to suppress S. aureus-induced irreversible joint damage.

Enhancing early detection of neurological and developmental disorders and provision of intervention in low-resource settings in Uttar Pradesh, India: study protocol of the G.A.N.E.S.H. programme.

INTRODUCTION: Around 9% of India's children under six are diagnosed with neurodevelopmental disorders. Low-resource, rural communities often lack programmes for early identification and intervention. The Prechtl General Movement Assessment (GMA) is regarded as the best clinical tool to predict cerebral palsy in infants <5 months. In addition, children with developmental delay, intellectual disabilities, late detected genetic disorders or autism spectrum disorder show abnormal general movements (GMs) during infancy. General Movement Assessment in Neonates for Early Identification and Intervention, Social Support and Health Awareness (G.A.N.E.S.H.) aims to (1) provide evidence as to whether community health workers can support the identification of infants at high-risk for neurological and developmental disorders and disabilities, (2) monitor further development in those infants and (3) initiate early and targeted intervention procedures. METHODS: This 3-year observational cohort study will comprise at least 2000 infants born across four districts of Uttar Pradesh, India. Community health workers, certified for GMA, video record and assess the infants' GMs twice, that is, within 2 months after birth and at 3-5 months. In case of abnormal GMs and/or reduced MOSs, infants are further examined by a paediatrician and a neurologist. If necessary, early intervention strategies (treatment as usual) are introduced. After paediatric and neurodevelopmental assessments at 12-24 months, outcomes are categorised as normal or neurological/developmental disorders. Research objective (1): to relate the GMA to the outcome at 12-24 months. Research objective (2): to investigate the impact of predefined exposures. Research objective (3): to evaluate the interscorer agreement of GMA. ETHICS AND DISSEMINATION: G.A.N.E.S.H. received ethics approval from the Indian Government Chief Medical Officers of Varanasi and Mirzapur and from the Ramakrishna Mission Home of Service in Varanasi. GMA is a worldwide used diagnostic tool, approved by the Ethics Committee of the Medical University of Graz, Austria (27-388 ex 14/15). Apart from peer-reviewed publications, we are planning to deploy G.A.N.E.S.H. in other vulnerable settings.