FGF23-secreting sinonasal tumour presenting with acute subdural haemorrhage and tumour-induced osteomalacia.

A female in her 50s developed a headache, collapsed and was noted to have an acute atraumatic subdural haemorrhage (SDH) requiring surgical evacuation and intracranial pressure-directed therapy. Her background included recurrent epistaxis, severe generalised bone pain and multiple insufficiency fractures and an undifferentiated autoimmune connective tissue disease. Chronic hypophosphataemia, elevated alkaline phosphatase and raised fibroblast growth factor 23 (FGF23) were also noted. An MRI head and subsequent 68Ga CT/positron emission tomography scan demonstrated an intensely avid tumour in the right ethmoid sinus, extending intracranially. Phosphate was aggressively replaced, and alfacalcidol was initiated to circumvent the effects of FGF23 on her kidneys and bone minerals. The tumour was biopsied and then definitively resected via combined endonasal and craniotomy approaches, resulting in good clinical improvement. FGF23 titre and serum phosphate both normalised leaving the diagnosis of a phosphaturic mesenchymal tumour-secreting FGF23, leading to tumour-induced osteomalacia.

French-language questionnaires in ENT: Inventory and review.

OBJECTIVE: Patient-Reported Outcome Measures (PROMs) are now an integral part of clinical and academic practice in ENT, and it is essential to have tools with a validated French version. However, there are no guidelines on ENT questionnaires available in French or those that could have transcultural adaptation. METHODS: The present study, under the auspices of the ENT National Professional Council and the French Society of ENT, inventoried PROMs, for each super-specialty and pathology, meeting one of the following inclusion criteria: validated French version, not translated but used internationally (i.e., translated into other languages and widely cited since 2017), or subjectively deemed useful by experts in the super-specialty in question. RESULTS: In total, 103 questionnaires were identified. To encourage and accompany their intercultural adaptation and statistical validation, this article presents the rationale and methodology of such an undertaking. CONCLUSION: PROMs either already validated in French or which it would be useful to translate were inventoried. The methodology of translation and validation to guarantee reliability and relevance is presented.

Structurally Diverse ent-Clerodanoids from the Aerial Parts of Isodon scoparius.

Scoparodane C (1), a diterpenoid with a rare 3,4-seco-3-nor-2,11-epoxy-ent-clerodane scaffold, was obtained from the aerial parts of Isodon scoparius, along with isocopariusines A-E (2-6), five ent-clerodanoids featuring a 5/6-fused ring system, and isocopariusines F-H (7-9), three common ent-clerodanoids. The structures of these previously undescribed compounds were established by a combination of spectroscopic analysis, X-ray diffraction, chemical derivatization, and quantum chemical calculation. Remarkably, isocopariusine B (3) showed strong resistance reversal activity against fluconazole-resistant Candida albicans.

Evidence of bottom-up homeostatic modulation induced taVNS during emotional and Go/No-Go tasks.

Bilateral transcutaneous auricular vagus nerve stimulation (taVNS) - a non-invasive neuromodulation technique - has been investigated as a safe and feasible technique to treat many neuropsychiatric conditions. such as epilepsy, depression, anxiety, and chronic pain. Our aim is to investigate the effect of taVNS on neurophysiological processes during emotional and Go/No-Go tasks, and changes in frontal alpha asymmetry. We performed a randomized, double-blind, sham-controlled trial with 44 healthy individuals who were allocated into two groups (the active taVNS group and the sham taVNS group). Subjects received one session of taVNS (active or sham) for 60 min. QEEG was recorded before and after the interventions, and the subjects were assessed while exposed to emotional conditions with sad and happy facial expressions, followed by a Go/No-Go trial. The results demonstrated a significant increase in N2 amplitude in the No-Go condition for the active taVNS post-intervention compared to the sham taVNS after adjusting by handedness, mood, and fatigue levels (p = 0.046), significantly reduced ERD during sad conditions after treatment (p = 0.037), and increased frontal alpha asymmetry towards the right frontal hemisphere during the emotional task condition (p = 0.046). Finally, we observed an interesting neural signature in this study that suggests a bottom-up modulation from brainstem/subcortical to cortical areas as characterized by improved lateralization of alpha oscillations towards the frontal right hemisphere, and changes in ERP during emotional and Go/No-Go tasks that suggests a better subcortical response to the tasks. Such bottom-up effects may mediate some of the clinical effects of taVNS.

Unusual case of Reinke's oedema.

This case report describes a man in his mid 40s, with a history of chronic smoking, who presented with dysphonia. He underwent microlaryngoscopy and biopsy for a suspicious lesion on the anterior right vocal cord. Mask ventilation proved difficult on induction of general anaesthesia due to a solid lesion acting as a ball valve into the glottis. This mass was LASER debulked and sent for histopathology. This demonstrated a haematoma, likely traumatic in origin, with some polypoidal features, consistent with advanced Reinke's oedema. Reinke's oedema is a benign condition where chronic inflammation causes fluid accumulation within the vocal cords. Long-standing inflammation leads to disarrangement of the vocal cord lamina propria, causing fluid accumulation and thereby resulting oedema of the vocal cords. This process can subsequently lead to polyp formation and can cause gravelly voice. This case report describes the potential airway sequelae of this benign condition.

Assessing the Effectiveness of Voice Therapy Techniques in Treating Dysphonia: An Otolaryngological Review.

Dysphonia is a prevalent condition that can impact individuals across all age groups. It occurs when normal voice quality is altered, caused by structural and/or functional issues. Evaluation and assessment from clinicians are warranted if dysphonia persists for more than four weeks and/or is coupled with risk factors or other concerning clinical manifestations. Additionally, voice disorders can increase the risk of depression and anxiety disorders, as well as raise stress levels and lower self-reported health indicators. Dysphonia can have a substantial influence on interpersonal interactions and lower overall quality of life since effective communication relies significantly on spoken language. Hence, managing dysphonia is essential for enhancing communication abilities, improving quality of life, maintaining vocational functioning, promoting psychological well-being, and addressing underlying health concerns. Speech and language therapy, medical management, surgery, or a combination of the aforementioned are all possible treatments for dysphonia. Speech and language therapy is often the first-line treatment option for dysphonia patients who do not meet the criteria for surgical intervention. Voice therapy is often beneficial and remains the first line of treatment, even when patients approach with benign vocal fold nodules. A well-designed voice therapy program improves both the quality of life and vocal performance. The majority of the studies in the existing literature advocate for and report beneficial outcomes associated with voice therapy; however, more research is needed to provide evidence-based findings to guide clinical practice and achieve optimal outcomes. This comprehensive review elaborately highlights the utilization and efficacy of various voice therapeutic modalities utilized for the management of dysphonia in light of current literature.

Characterization of Equilibrative Nucleoside Transport of the Pancreatic Cancer Cell Line: Panc-1.

Objectives: Gemcitabine, a first-line chemotherapeutic nucleoside analog drug (NAD) for pancreatic cancer, faces limitations due to drug resistance. Characterizing pancreatic cancer cells' transport characteristics may help identify the mechanisms behind drug resistance, and develop more effective therapeutic strategies. Therefore, in this study, we aimed to determine the nucleoside transport properties of Panc-1 cells, one of the commonly used pancreatic adenocarcinoma cell lines. Materials and Methods: To assess the presence of equilibrative nucleoside transporter-1 (ENT-1) in Panc-1 cells, we performed immunofluorescence staining, western blot analysis, and S-(4-nitrobenzyl)-6-thioinosine (NBTI) binding assays. We also conducted standard uptake assays to measure the sodium-independent uptake of [3H]-labeled chloroadenosine, hypoxanthine, and uridine. In addition, we determined the half-maximal inhibitory concentration (IC50) of gemcitabine. Statistical analyses were performed using GraphPad Prism version 8.0 for Windows. Results: The sodium-independent uptake of [3H]-labeled chloroadenosine, hypoxanthine, and uridine was measured using standard uptake assays, and the transport rates were determined as 111.1 ± 3.4 pmol/mg protein/10 s, 62.5 ± 4.8 pmol/mg protein/10 s, and 101.3 ± 2.5 pmol/mg protein/10 s, respectively. Furthermore, the presence of ENT-1 protein was confirmed using NBTI binding assays (Bmax 1.52 ± 0.1 pmol/mg protein; equilibrium dissociation constant 0.42 ± 0.1 nM). Immunofluorescence assays and western blot analysis also revealed ENT-1 in Panc-1 cells. The determined IC50 of gemcitabine in Panc-1 cells was 2 µM, indicating moderate sensitivity. Conclusion: These results suggest that Panc-1 is a suitable preclinical cellular model for studying NAD transport properties and potential therapies in pancreatic cancer and pharmaceutical research.

Granulomatosis With Polyangiitis as an Etiology of Silent Sinus Syndrome: A Case Report.

Silent sinus syndrome (SSS) is a rare condition characterized by the collapse of the maxillary sinus and the sinking of the eye socket (enophthalmos). Only around 100 cases of SSS have been reported so far. The underlying cause of this condition is the chronic obstruction of the osteomeatal complex, which leads to sinus contraction. In this case, we present a novel finding linking SSS with granulomatosis with polyangiitis (GPA). The patient described is a 39-year-old male who was diagnosed with SSS after a prolonged period of sinus pressure, headaches, epistaxis, and generalized congestion. Additionally, the patient reported a significant autoimmune history, including a previous occurrence of ANCA-mediated glomerulonephritis. Surgical intervention revealed the presence of significant granulation tissue, while histopathological examination identified areas of necrosis, vasculitis, and multinucleated giant cells consistent with GPA. This finding was further supported by the detection of positive blood c-ANCA. This case is particularly noteworthy as it is the first reported instance of GPA causing SSS. It serves as an excellent example to illustrate the underlying pathophysiology of SSS.

Silent threat of isolated sphenoid sinus tuberculosis resulting in blindness and ophthalmoplegia.

A diabetic woman in her fifties presented with a sudden onset of failing vision and diplopia involving the right eye for two days, along with fever and headache. Radiological investigations revealed right sphenoid sinusitis along with inflammation around the right orbital apex and optic nerve. Functional endoscopic sinus surgery, with orbital and optic nerve decompression improved the ocular movements, but not the visual acuity. Histopathology was suggestive of a granulomatous inflammatory lesion, and high-resolution computed tommography (HRCT) of the thorax revealed lung lesions suggestive of an old tubercular infection, and antitubercular treatment (ATT) was then initiated.At the end of two months of ATT, there was complete resolution of ophthalmoplegia, relative afferent pupillary defect, direct and consensual light reflex however, failure of improvement in her visual acuity, indicated damage to the optic nerve.Extrapulmonary tuberculosis involving an isolated sphenoid sinus is rare and elusive. Prompt radiological investigations, followed by orbital decompression and ATT, provide the best possible outcomes.

Exploring the potential of omics technologies in medicinal plant research: a review in Colombia / Explorando el potencial de las tecnologías ómicas en la investigación de plantas medicinales: una revisión en Colombia

This review presents advances in the implementation of high - throughput se quencing and its application to the knowledge of medicinal plants. We conducted a bibliographic search of papers published in PubMed, Science Direct, Google Scholar, Scopus, and Web of Science databases and analyzed the obtained data using VOSviewer (versi on 1.6.19). Given that medicinal plants are a source of specialized metabolites with immense therapeutic values and important pharmacological properties, plant researchers around the world have turned their attention toward them and have begun to examine t hem widely. Recent advances in sequencing technologies have reduced cost and time demands and accelerated medicinal plant research. Such research leverages full genome sequencing, as well as RNA (ribonucleic acid) sequencing and the analysis of the transcr iptome, to identify molecular markers of species and functional genes that control key biological traits, as well as to understand the biosynthetic pathways of bioactive metabolites and regulatory mechanisms of environmental responses. As such, the omics ( e.g., transcriptomics, metabolomics, proteomics, and genomics, among others) have been widely applied within the study of medicinal plants, although their usage in Colombia is still few and, in some areas, scarce. (185)

El extracto de cloroformo (CE) y las fracciones obtenidas de las raíces de Aldama arenaria se evaluaron para determinar su actividad antiproliferativa in vitro contra 10 líneas ce lulares tumorales humanas [leucemia (K - 562), mama (MCF - 7), ovario que expresa un fenotipo resistente a múltiples fármacos (NCI/ADR - RES), melanoma (UACC - 62), pulmón (NCI - H460), próstata (PC - 3), colon (HT29), ovario (OVCAR - 3), glioma (U251) y riñón (786 - 0)]. CE presentó actividad antiproliferativa débil a moderada (log GI 50 medio 1.07), mientras que las fracciones 3 y 4, enriquecidas con diterpenos de tipo pimarane [ent - pimara - 8 (14), ácido 15 - dien - 19 - oico y ent - 8(14),15 - pimaradien - 3 ß - ol], presentaron activid ad moderada a potente para la mayoría de las líneas celulares, con un log GI 50 medio de 0.62 y 0.59, respectivamente. Los resultados mostraron una acción antiproliferativa in vitro prometedora de las muestras obtenidas de A. arenaria , con los mejores resul tados para NCI/ADR - RES, HT29 y OVCAR - 3, y valores de TGI que van desde 5.95 a 28.71 µg.mL - 1, demostrando que los compuestos de esta clase pueden ser prototipos potenciales para el descubrimiento de nuevos agentes terapéuticos

Deep Brain Stimulation Inhibits Epileptic Seizures via Increase of Adenosine Release and Inhibition of ENT1, CD39, and CD73 Expression.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39, and CD73 are involved in the mechanism of DBS for epilepsy. A total of 48 SD male rats were divided into four groups: control (naïve rats), Pilo (pilocarpine induced rats with epilepsy), DBS (rats with epilepsy treated with DBS for 8 weeks), and sham. In the present study, video electroencephalogram monitoring, Morris water maze assays, in vivo measurements of adenosine using fiber photometry, histochemistry, and western blot were performed on the hippocampus. DBS markedly attenuated spontaneous recurrent seizures (SRSs) and enhanced spatial learning in rats with epilepsy, assessed through video-EEG and water maze assays. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. The expressions of ENT1, CD39, and CD73 in Pilo group and sham group increased compared with the control group, while the expressions of ENT1, CD39, and CD73 in DBS group decreased compared to that of Pilo group and sham group. The findings indicate that DBS reduces the number of SRSs and improves spatial memory in rats with epilepsy with concomitant decrease of ENT1, CD39, and CD73 expressions. Adenosine-modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.

Design and synthesis of 6,20-epoxy A-ring modified oridonin derivatives with antitumor activity through extrinsic and mitochondrial pathways.

Oridonin is an antitumor ent-kaurane diterpenoid that medicinal chemists have been paying close attention to in recent years. Herein, a novel 6,20-epoxy A-ring modified oridonin derivative 2 was obtained by a 6-step synthesis. A series of 14-O derivatives of 2 (EpskA1-EpskA24) were synthesized to further enhance the activity. Based on their cytotoxicity against MCF-7, A549 and L-02 cells, EpskA9, EpskA10 and EpskA21 were chosen for further screening to obtain a wider antitumor spectrum. Collectively, EpskA21 showed the most potent antiproliferative activity, inhibiting proliferation and migration, and inducing apoptosis and cell cycle arrest in MCF-7 and MIA-PaCa-2 cells. With the help of network pharmacology analysis, apoptosis-related proteins were selected and further tested by western blot assay. The inhibition of PI3K/AKT and an increase in the levels of Bax/Bcl-2 ratio, Cyt-C, cleaved-Caspase-9, cleaved-Caspase-3 and cleaved-PARP was observed, indicating that EpskA21 induced apoptosis through the mitochondrial pathway. Given that an increase in DR5 expression and activated Caspase-8 were also observed, the extrinsic apoptosis pathway might also be related to the antitumor effect.

Screening of ent-copalyl diphosphate synthase and metabolic engineering to achieve de novo biosynthesis of ent-copalol in Saccharomyces cerevisiae.

The diterpene ent-copalol is an important precursor to the synthesis of andrographolide and is found only in green chiretta (Andrographis paniculata). De novo biosynthesis of ent-copalol has not been reported, because the catalytic activity of ent-copalyl diphosphate synthase (CPS) is very low in microorganisms. In order to achieve the biosynthesis of ent-copalol, Saccharomyces cerevisiae was selected as the chassis strain, because its endogenous mevalonate pathway and dephosphorylases could provide natural promotion for the synthesis of ent-copalol. The strain capable of synthesizing diterpene geranylgeranyl pyrophosphate was constructed by strengthening the mevalonate pathway genes and weakening the competing pathway. Five full-length ApCPSs were screened by transcriptome sequencing of A. paniculata and ApCPS2 had the best activity and produced ent-CPP exclusively. The peak area of ent-copalol was increased after the ApCPS2 saturation mutation and its configuration was determined by NMR and ESI-MS detection. By appropriately optimizing acetyl-CoA supply and fusion-expressing key enzymes, 35.6 mg/L ent-copalol was generated. In this study, de novo biosynthesis and identification of ent-copalol were achieved and the highest titer ever reported. It provides a platform strain for the further pathway analysis of andrographolide and derivatives and provides a reference for the synthesis of other pharmaceutical intermediates.

Pre-Operative Planning of a DCR Surgery Using Virtual Reality.

PURPOSE: To assess a novel Virtual Reality (VR) tool designed to enhance understanding of the nasal anatomy in patients eligible for DCR surgery. METHODS: Preoperative Computed Tomography (CT) scans of the orbit were obtained and loaded as DICOM (Digital Imaging and Communications in Medicine) files onto the D2P software (3D Systems Inc. Littleton, CO) for tissue segmentation and 3D model preparation. Segmentation was performed on several anatomical structures, including the skull, lacrimal sac, nasal septum, inferior and middle turbinate. The resulting 3D model was visualized using a VR headset. After completing the segmentation procedure, ten cases were evaluated by a panel of six surgeons, including both senior and resident physicians from ENT and oculoplastic specialties. RESULTS: The dataset under examination comprised images from 10 preoperative CT scans of the orbits of patients eligible for Endo-DCR. When evaluating the CT using the VR tool, in 73.3% of the cases ENT surgeons were right about the side of pathology, while only 43.3% ophthalmologists were right (chi-square, p = .018). In 72.8% of the cases ENT surgeons were evaluated right that there is a septum deviation, while only in 47.2% of the cases the ophthalmologists were right (chi-square, p = .094).When evaluating the CT using the VR tool, in 60% of the cases consultants were right about the pathology, while 57.7% of the residents were right (chi-square, p = .853). In 81.7% of the cases consultants were evaluated right that there is a septum deviation, while only in 58.3% of the cases the ophthalmologists were right (chi-square, p = .198). DISCUSSION: ENT surgeons, as well as consultants, interpreted the CT better than the ophthalmologists and residents. Surprisingly, the VR system did not help them to interpret the CT better. Further, more extensive studies should be done to build a VR system that assists in the correct interpretation of the preoperative CT before DCR surgery as well as during DCR surgery.

Laryngeal schwannoma masquerading as malignancy.

Laryngeal schwannoma is a rare type of neurogenous tumour with a non-specific presentation. We present a case of a middle-aged man with issues of hoarseness, globus sensation and intermittent episodes of throat pain. The Hopkins examination showed right vocal fold irregularity with fullness in the right ventricle. The contrast-enhanced CT neck revealed an ill-defined lesion with contrast uptake extending into the paraglottic region with no neck node involvement. Considering the clinical presentation of hoarseness, throat pain and globus with imaging revealing contrast enhancement of lesion, direct laryngoscopy and biopsy were planned to rule out malignancy. Intraoperatively, a well-defined submucosal capsulated swelling became apparent after incision and dissection of the mucosa over the right vocal fold. A complete excision of the swelling was done with microlaryngeal instruments without tracheostomy. The histopathological report was suggestive of schwannoma. The literature review discusses clinical presentation, location, imaging features and management strategy.

Improving the Quality and Standardization of Operative Notes in a Tertiary Regional ENT Department: A Closed-Loop Audit.

INTRODUCTION: Comprehensive and accurate documentation is paramount in ensuring patient safety, and continuity of care, and casts the foundation for auditing practice and creating research. Unfortunately, a lack of documentation has been reported globally. This study aims to challenge current practices and ensure high-quality documentation. METHODOLOGY: The study appraised 100 operation notes completed within a tertiary, regional ENT department against the published guidance. Following an inquiry into the findings, the operative note proformas were modified in alignment with the Royal College of Surgeons (RCS) published standards for the quality of operative notes. A further 100 operation notes were audited. Rates of compliance before and post implementing the intervention were compared. Non-parametric data were analyzed using Fischer's exact test, with P < 0.05 considered to be statistically significant. RESULTS: Upon auditing of operative note completeness against the set criteria, the use of a comprehensive operative note proforma significantly refined the quality of documentation and adherence to the published standards (P < 0.00001). CONCLUSIONS: This study displayed the lack of adherence to the RCS standards about the quality of operative notes within our center. The adoption of a modified proforma which incorporates the 18 criteria defined by the RCS resulted in improved conformance to published standards and a higher quality of documentation. This study corroborates the RCS framework as an effective tool in recognizing deficient practices and areas of improvement. Through compliance with published standards, a higher quality of documentation is attained, contributing to patient safety, clear continued communication, and support of clinical governance.

[About a case of primary laryngeal mucosal melanoma in a patient with medical history of oropharyngeal squamous carcinoma]. / À propos d'un cas de mélanome muqueux primitif laryngé chez un patient présentant un antécédent de carcinome épidermoïde de l'oropharynx.

INTRODUCTION: Primary laryngeal mucosal melanoma is a rare tumour with a poor prognosis. Its often difficult diagnosis should rule out laryngeal metastatic localization of cutaneous melanoma. CASE PRESENTATION: We report a case of primary laryngeal mucosal melanoma diagnosed in a 65-year-old man, treated 6 years previously with radio-chemotherapy and surgery for squamous cell carcinoma of the right lateral oropharyngeal region. The definitive diagnosis of primary laryngeal mucosal melanoma was made on the resection specimen, whereas the initial biopsy of the epilaryngeal mass discovered during the patient's surveillance had concluded that it was a laryngeal recurrence of the known squamous cell carcinoma. DISCUSSION: Through this case, we propose to remind the main characteristics and the diagnostic pitfalls of these tumours.