Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy.

The most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions. We found a weak negative correlation between tissue cellularity and the fluorescence intensity of PpIX across all imaged specimens. Semi-supervised clustering of the TPEF images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses of the imaged tissue showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of external spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets from glioblastoma specimens confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings question 5-ALA-induced fluorescence in glioma cells and show how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of gliomas.

Mucocutaneous Leishmaniasis Rhinology Complications: A Rare Presentation.

OBJECTIVE: This case report presents a unique manifestation of Mucocutaneous Leishmaniasis (MCL) in a 56-year-old woman with chronic nasal symptoms. Initially diagnosed with chronic sinusitis and septal perforation, the patient's history of a childhood sandfly bite and subsequent episodes of Leishmaniasis, revealed after nasal surgery, provided crucial information for accurate diagnosis. METHODS: A retrospective review was conducted on this patient's electronic medical record. RESULTS: The patient's life-long struggle with nasal obstruction, congestion, and a septal perforation initially masked the underlying MCL. Sinus surgery and persistent symptoms further complicated the diagnostic process. Only after postoperative complications, including grainy skin texture extending into the nasal passages, did the patient recall the sandfly bite, prompting reevaluation and diagnosis of MCL. The case highlights the challenges of diagnosing MCL due to its varied presentation and potential mimicry of other chronic nasal conditions. It emphasizes the importance of thorough patient history-taking, especially when symptoms are atypical or persistent. Additionally, the report underscores the potential for unexpected postoperative complications in MCL patients and the need for vigilance in recognizing and assessing them. CONCLUSION: This case contributes to the understanding of MCL's diverse clinical presentation and the importance of early diagnosis and multidisciplinary management for prompt intervention and improved outcomes.

The impact of frailty on facial nerve recovery following Bell's palsy.

OBJECTIVES: Patients with Bell's palsy, the sudden onset of facial paralysis, have variable recovery. Frailty has been recognized as an important factor in predicting recovery. This study investigated the relationship between frailty and facial nerve recovery in Bell's palsy patients. METHODS: A retrospective review was conducted on 95 Bell's palsy patients at a single institution's Department of Otolaryngology from 2014 to 2023. A clinically relevant facial nerve recovery was defined as a House-Brackmann (HB) score decrease>1 between the initial and most recent visit. Patients without follow-up visits or initial HB scores <3 were excluded. Frailty was measured by modified frailty index-5 (mFI-5) at the time of Bell's palsy diagnosis. Elderly patients were those over 65 years at presentation (n = 29). Frail patients had mFI-5 > 1 (n = 8). Chi-squared analyses, Fisher's exact tests, and logistic regression models were conducted in SPSS. RESULTS: The analytic sample included 95 patients (median age = 56.8 years, IQR = 24.1) presenting with an initial HB score > 2. 36 % of patients' HB scores decreased by ≥2 within the follow-up period. Frailty (unadjusted Odds Ratio (OR) = 6.3, 95 % CI = [1.2, 33.1], p = .023) was associated with facial nerve recovery while age was not (unadjusted OR = 1.07, 95 % CI = [0.44, 2.59], p = .889). The mFI-5 adjusted OR was 8.43 (95 % CI = [1.38, 51.4], p = .021) when adjusting for age, gender, treatment modality, access to care, and follow-up duration in a logistic regression. CONCLUSIONS: Frailty correlated with enhanced facial nerve recovery after Bell's palsy in this cohort; age was not significantly associated. Further investigation into factors associated with frailty, including increased surveillance and treatment frequency, is warranted.

ATP Synthase and Mitochondrial Bioenergetics Dysfunction in Alzheimer's Disease.

Alzheimer's Disease (AD) is the most common neurodegenerative disorder in our society, as the population ages, its incidence is expected to increase in the coming decades. The etiopathology of this disease still remains largely unclear, probably because of the highly complex and multifactorial nature of AD. However, the presence of mitochondrial dysfunction has been broadly described in AD neurons and other cellular populations within the brain, in a wide variety of models and organisms, including post-mortem humans. Mitochondria are complex organelles that play a crucial role in a wide range of cellular processes, including bioenergetics. In fact, in mammals, including humans, the main source of cellular ATP is the oxidative phosphorylation (OXPHOS), a process that occurs in the mitochondrial electron transfer chain (ETC). The last enzyme of the ETC, and therefore the ulterior generator of ATP, is the ATP synthase. Interestingly, in mammalian cells, the ATP synthase can also degrade ATP under certain conditions (ATPase), which further illustrates the crucial role of this enzyme in the regulation of cellular bioenergetics and metabolism. In this collaborative review, we aim to summarize the knowledge of the presence of dysregulated ATP synthase, and of other components of mammalian mitochondrial bioenergetics, as an early event in AD. This dysregulation can act as a trigger of the dysfunction of the organelle, which is a clear component in the etiopathology of AD. Consequently, the pharmacological modulation of the ATP synthase could be a potential strategy to prevent mitochondrial dysfunction in AD.