WNT5B drives osteosarcoma stemness, chemoresistance and metastasis.

BACKGROUND: Treatment for osteosarcoma, a paediatric bone cancer with no therapeutic advances in over three decades, is limited by a lack of targeted therapies. Osteosarcoma frequently metastasises to the lungs, and only 20% of patients survive 5 years after the diagnosis of metastatic disease. We found that WNT5B is the most abundant WNT expressed in osteosarcoma tumours and its expression correlates with metastasis, histologic subtype and reduced survival. METHODS: Using tumor-spheroids to model cancer stem-like cells, we performed qPCR, immunoblotting, and immunofluorescence to monitor changes in gene and protein expression. Additionally, we measured sphere size, migration and forming efficiency to monitor phenotypic changes. Therefore, we characterised WNT5B's relevance to cancer stem-like cells, metastasis, and chemoresistance and evaluated its potential as a therapeutic target. RESULTS: In osteosarcoma cell lines and patient-derived spheres, WNT5B is enriched in stem cells and induces the expression of the stemness gene SOX2. WNT5B promotes sphere size, sphere-forming efficiency, and cell proliferation, migration, and chemoresistance to methotrexate (but not cisplatin or doxorubicin) in spheres formed from conventional cell lines and patient-derived xenografts. In vivo, WNT5B increased osteosarcoma lung and liver metastasis and inhibited the glycosaminoglycan hyaluronic acid via upregulation of hyaluronidase 1 (HYAL1), leading to changes in the tumour microenvironment. Further, we identified that WNT5B mRNA and protein correlate with the receptor ROR1 in primary tumours. Targeting WNT5B through inhibition of WNT/ROR1 signalling with an antibody to ROR1 reduced stemness properties, including chemoresistance, sphere size and SOX2 expression. CONCLUSIONS: Together, these data define WNT5B's role in driving osteosarcoma cancer stem cell expansion and methotrexate resistance and provide evidence that the WNT5B pathway is a promising candidate for treating osteosarcoma patients. KEY POINTS: WNT5B expression is high in osteosarcoma stem cells leading to increased stem cell proliferation and migration through SOX2. WNT5B expression in stem cells increases rates of osteosarcoma metastasis to the lungs and liver in vivo. The hyaluronic acid degradation enzyme HYAL1 is regulated by WNT5B in osteosarcoma contributing to metastasis. Inhibition of WNT5B with a ROR1 antibody decreases osteosarcoma stemness.

Short Comprehensive Multimodal Behavioural Intervention for Tuberculosis-Can It Be Effectively Incorporated in Tribal Health?

BACKGROUND: Tuberculosis management in tribal areas is a major challenge to the National Tuberculosis Elimination Program in India. There is need for culturally appropriate interventions for bridging the gaps existing in the current system. There is paucity of research in this vulnerable group; hence, a study was undertaken to determine the effect of a Short Comprehensive Multimodal Behavioural Intervention in tribal colonies of Kerala. METHODS: The study used before-after design to assess the effectiveness of a Short Comprehensive Multimodal Behavioural Intervention for tuberculosis knowledge and voluntary reporting among residents of tribal colonies. The intervention included individual, small group, and large group education, with verbal, printed, and performance methods. Public-private partnership with community participation was emphasized to encourage the residents to approach public health system for managing tuberculosis. RESULTS: Ten tribal colonies from two districts were included with 104 participants. There was significant improvement in the proportion of participants with knowledge regarding different aspects of tuberculosis such as aetiology, symptoms, transmission, and treatment. The overall knowledge score had a significant improvement [median (range) 3.0 (0-9) to 7.0 (0-11), p < 0.001] when assessed one month consequent to the intense period of group education. CONCLUSION: Short-term health behavioural intervention package appropriate for the target group, implemented with public-private partnership and community participation of trained local volunteers, proved effective in improving the knowledge regarding tuberculosis and thereby health-seeking behaviour in detection. This can be tested for scaling up, and replication in other tribal health issues.

A facile route to synthesize n-SnO2/p-CuFe2O4 to rapidly degrade toxic methylene blue dye under natural sunlight.

In the present study, the n-SnO2/p-CuFe2O4 (p-CFO) complex was prepared by a two-step process. p-CFO synthesized by the molten salt method was coated with SnO2 synthesized by a facile in situ chemical precipitation method. The formation of n-SnO2/p-CFO was confirmed by powder X-ray diffraction (PXRD). Scanning electron microscopy (SEM) images showed that the sharp edges of uncoated pyramid-like p-CFO particles were covered by a thick layer of n-SnO2 on coated p-CFO particles. The complete absence of Cu and only 3 wt% Fe on the surface of the n-p complex observed in the elemental analysis using energy-dispersive X-ray spectroscopy (EDX) on the n-p complex confirmed the presence of a thick layer of SnO2 on the p-CFO surface. Diffuse reflectance spectroscopy (DRS) was employed to elucidate the bandgap engineering. The n-SnO2/p-CFO complex and p-CFO showed 87% and 58.7% methylene blue (MB) degradation in 120 min under sunlight, respectively. The efficiency of the n-p complex recovered after 5 cycles (73.5%) and was found to be higher than that of the uncoated p-CFO (58.7%). The magnetically separable property of the n-p complex was evaluated by using vibration sample magnetometry (VSM) measurements and it was confirmed that the prepared photocatalyst can be easily recovered using an external magnet. The study reveals that the prepared complex could be a potential candidate for efficient photodegradation of organic dyes under sunlight due to its efficient recovery and reusability owing to its magnetic properties.

A randomized clinical trial comparing the King Vision (channeled blade) and the CMAC (D blade) videolaryngoscopes in patients with cervical spine immobilization.

Background and Aims: Cervical spine immobilization renders direct laryngoscopy difficult. The CMAC D blade and the channeled blade of the King Vision videolaryngoscopes, have both been used for difficult airway management. Our hypothesis is that the channeled blade of the King Vision would be superior to the CMAC D blade in terms of ease of intubation. We tested this hypothesis in a randomized comparison of the two videolaryngoscopes in patients with simulated cervical spine immobilization. Material and Methods: Hundred patients with no anticipated airway difficulty were randomly allocated to two groups after obtaining informed written consent. Following induction, manual inline stabilization (MILS) was applied to simulate a cervical spine injury and immobilzation. Patients were intubated with either of the two videolaryngoscopes. Time for visualization of the glottis, procedural time, intubation difficulty scale (IDS), and hemodynamic response were recorded. Results: The time to visualize the glottis was shorter in the CMAC D group as compared to the King Vision group (P < 0.001). The incidence of external laryngeal manipulation was less in the King Vision group (P < 0.001). The ease of intubation was superior in the King Vision group, based on the IDS (P < 0.001). The haemodynamic response was similar between the groups. Conclusion: King Vision channeled videolaryngoscope was difficult to introduce into the mouth of the patient during laryngoscopy. Once introduced into the mouth, the time for intubation was less and less external laryngeal manipulation maneuvers were performed to achieve successful intubation. The ease of endotracheal intubation was superior for the King Vision videolaryngoscope. The King Vision videolaryngoscope with proper tranining, could be a safe and portable alternative in patients with cervical spine immobilization.

Assessment of craniocervical posture in TMJ disorders using lateral radiographic view: A cross-sectional study.

Objective: To determine the craniocervical posture in 120 subjects, 90 patients with temporo- mandibular joint disorders (TMD) of varying degrees were selected and compared with those of 30 healthy individuals.Methods: True lateral radiographs in the natural head position were obtained from TMD patients and healthy individuals. Linear measurements from the opisthion to the intersecting point of the craniovertebral angle, the opisthion to the tip of the spinous process of the seventh cervical vertebrae, and the body of Atlas to the lower border of the seventh cervical vertebrae were obtained. Data were analyzed by one way ANOVA followed by Scheffe's post hoc test.Results: Significant increases in craniovertebral, odontoid plane, and individual vertebral angles were noted in the TMD patients when compared with the healthy individuals.Conclusion: Significant postural changes in the skull in relation to the cervical vertebrae with dorsiflexion as a compensatory strategy were observed in this study.

Cerebral Protection Using Percutaneous Normothermic Bilateral Antegrade Cerebral Perfusion During Total Arch TEVAR in a Patient With Shaggy Aorta.

Purpose: To report a technique of global cerebral embolic protection (CEP) designed for use during thoracic endovascular aortic repair (TEVAR). Technique: Arterial cannulas are inserted percutaneously in the right axillary artery (12-F) and left common carotid artery (LCCA; 10-F) to provide normothermic antegrade cerebral perfusion during TEVAR with neuromonitoring. Inferior vena cava blood is drawn using a 19-F femoral cannula, filtered, oxygenated, and delivered through independent roller pumps to the arterial cannulas. Static CEP is obtained by balloon occlusion of the 3 aortic arch branches proximally, resulting in complete separation of aortic and cerebral blood flow; static CEP is used during aortic endograft delivery and deployment. Dynamic CEP, obtained by creating flow reversal in the innominate artery and proximal LCCA, is used at all other times. Successful use of this CEP technique is illustrated in a patient with shaggy aorta undergoing fenestrated total arch TEVAR. Conclusion: Percutaneous normothermic bilateral antegrade cerebral perfusion provides effective CEP during TEVAR.

Comparative evaluation of hemodynamic responses and ease of intubation with airtraq video laryngoscope versus macintosh laryngoscope in patients with ischemic heart disease.

Introduction: Hemodynamic responses during laryngoscopy can potentially precipitate ischemia in patients with coronary artery disease. There are conflicting reports regarding the hemodynamic stress responses between the conventional Macintosh and video laryngoscopes. There is a paucity of studies regarding the same in cardiac surgical patients. Materials and Methods: A prospective, randomized control study to compare the hemodynamic responses and ease of intubation using Airtraq video laryngoscope and Macintosh laryngoscope in patients with ischemic heart disease. Results: Seventy patients were randomized into two groups. Baseline variables including age, weight, Mallampati score, and comorbidities were comparable between the two groups. There was statistically significant elevation in mean heart rate in the Macintosh group at 2nd-min (P = 0.02) and 3rd-min (P = 0.05) postintubation. Similarly, there was a significant increase in mean arterial pressure at 2nd (P = 0.06), 3rd (P = 0.03), and 4th (P = 0.03) in the Macintosh group. The time for laryngoscopy and Intubation Difficulty Scale was significantly better in the Airtraq group (P = 0.001 and 0.001). However, the median time to intubation was longer in the Airtraq group (13 s vs. 11 s, P = 0.05). Laryngoscopy view was better with Airtraq even in patients with Mallampati score 3 (ten patients). The incidence of trauma was same in both the groups. Conclusion: Airtraq provides the better hemodynamic stability and ease of intubation and may be considered superior to conventional Macintosh laryngoscope for intubation in patients with ischemic heart disease.

Attitude and Awareness of Dentists Practicing in Southern India Toward Non-steroidal Anti-inflammatory Drugs.

BACKGROUND: Pain management is an everyday challenge in dentistry. Analgesics are the group of drugs prescribed for effective pain management, of which nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs. Selection of NSAIDs must be judiciously made considering their pharmacological properties and adverse effects. AIM: This study aimed to analyze the attitude toward analgesic prescription among practicing dentists and the awareness to update their knowledge about them. MATERIALS AND METHODS: The study was carried out among 100 dental practitioners, where a questionnaire consisting of 16 questions was formulated based on the awareness of indication and contraindication, actual practice, and required future trends for updating the knowledge. The questionnaire was distributed among the practitioners; the answered questionnaire was collected and tabulated. Statistical analysis included χ2 test to evaluate the significance. RESULTS: Of 100 dental practitioners, 63% prescribed drugs based on the diagnosis. Aceclofenac was found to be the effective drug in postoperative pain management, whereas paracetamol was considered to be the safest among NSAIDs in clinical conditions such as bleeding disorders, gastric irritation, chronic kidney disease, and during pregnancy. All practicing dentists showed their willingness to participate in awareness programs in updating their knowledge. CONCLUSION: This study showed that dental clinical practitioners are well aware of the drugs to be prescribed in different clinical conditions but pitfalls have been observed in areas of systemic complication, where continuous educational programs are needed to overcome the same.

Usefulness of ultrasound-guided measurement of minimal transverse diameter of subglottic airway in determining the endotracheal tube size in children with congenital heart disease: A prospective observational study.

INTRODUCTION: The search for an accurate and predictable method to estimate the endotracheal tube (ETT) size in pediatric population had led to derivation of many formulae. Of this, age-based formulae are the most commonly used. Studies have shown that minimal transverse diameter of subglottic airway (MTDSA) measurements using a high-frequency probe improves the success rate of predicting the airway diameter to about 90%. We did a prospective observational study using MTDSA as the criteria to select the size of ETT in children with congenital heart disease. METHODS: In this prospective observational study, 51 children aged from 1 day to 5 years, scheduled for cardiac surgery, were enrolled for this study. The ETT size was guided solely based on the MTDSA. Leak test was used to determine the best-fit ETT size. RESULTS: Data from 49 patients were analyzed. Agreement between the ETT determined by MTDSA and that predicted by Cole's age-based formulas with the best-fit ETT size was analyzed using a Bland-Altman plot. CONCLUSION: Age-based formula showed poor correlation (27.5%) compared to MTDSA (87.8%) in predicting the best-fit ETT. We observed that pediatric patients with congenital heart disease need a larger sized ETT as compared to what was predicted by age-based formula. Using ultrasound MTDSA measurements to guide selection of ETT size is a safe and accurate method in pediatric cardiac population.

An innovative way to reinsert dislodged Arndt blocker using urological glide wire.

The Arndt blocker is positioned in the desired bronchus using a wire loop which couples the blocker with a fiberoptic bronchoscope (FOB). The wire loop once removed cannot be reinserted in 5F and 7F blockers making repositioning of the blocker difficult. A 34-year-old female was to undergo left thoracotomy followed by laparoscopic cholecystectomy. The left lung was isolated with a 7F Arndt bronchial blocker. During one-lung ventilation, the wire loop was removed for oxygen insufflation. There was loss of lung isolation during the procedure and dislodgement of the blocker was confirmed by FOB. The initial attempts to reintroduce the blocker into the left main bronchus failed. An alternative technique using a glide wire was attempted which resulted in successful reintroduction of the Arndt blocker. The 0.032 inch zebra glide wire may be effectively used to reposition a dislodged Arndt blocker if the wire loop has been removed.

Postlaryngectomy hypertensive crisis: a manifestation of perioperative acute baroreflex failure?

Hemodynamic instability as a result of altered baroreflex mechanism is common in surgeries involving manipulation around the carotid sheath. We report a case in which hypertensive crisis was associated with laryngectomy during general anesthesia. Perioperative use of vasoactive agents such as alpha(2) agonists may help in maintaining hemodynamic stability in such procedures.