L-lactate was long considered a glycolytic by-product but is now being recognized as a signaling molecule involved in cell survival. In this manuscript, we report the role of L-lactate in stress resistance and cell survival mechanisms using neuroblastoma cells (SH-SY5Y) as well as the C. elegans model. We observed that L-lactate promotes cellular defense mechanisms, including Unfolded Protein Response (UPR) and activation of nuclear factor erythroid 2–related factor 2 (NRF2), by promoting a mild Reactive Oxygen Species (ROS) burst. This increase in ROS triggers antioxidant defenses and pro-survival pathways, such as PI3K/AKT and Endoplasmic Reticulum (ER) chaperones. These results contribute to the understanding of the molecular mechanisms involved in beneficial effects of L-lactate, involving mild ROS burst, leading to activation of unfolded protein responses and detoxification mechanisms. We present evidence that this hormetic mechanism induced by L-lactate protects against oxidative stress in vitro and in vivo. This work contributes to the identification of molecular mechanisms, which could serve as targets for future therapeutic approaches for cell protection and aging-related disorders.

Enriched Pathways (ranked by p-value) a b PI3K/AKT pathway Diff. UP-regulated Diff. DOWN-regulated Pyruvate L-lactate 958 640 720 Pyruvate L-lactate 621 958 561

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Background: Current trends in medical curricula are shifting from teaching histology and pathology as stand-alone disciplines. Therefore, it would be useful to examine the potential value of integrating these into the anatomical dissection experience. Objectives: The aim of this study was to assess the histologic reliability of tissues taken from embalmed cadavers in an anatomy laboratory. Materials and Methods: A total of 112 tissue samples were obtained using standard autopsy techniques from various organs (heart, lung, thyroid, skeletal muscle, bone and skin) of 11 cadavers available at the anatomy laboratory of Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia, in 2019. Samples were prepared using the standard paraffin procedure followed by cutting sections at 4-μm thickness and staining with standard hematoxylin and eosin stain. Using predefined criteria, the quality of the samples was evaluated by two board-certified histopathologists and each slide was categorized as good, satisfactory or poor. Results: Overall, 34.2% and 60.3% of the slides were of good and satisfactory quality, respectively. A significant difference in tissue quality was found between various organs. Thick skin and bone tissues had the highest “good” rating (84.6% and 81.8%, respectively), while thyroid and lung tissues had the highest “poor” rating (20% and 13.6%, respectively). Conclusion: Most of the tissues acquired from the embalmed cadavers were of good or satisfactory quality, thereby indicating the beneficial use of histological tissue from cadavers for educational purposes. Future research into how these findings translate into meaningful medical education would be beneficial.

Background: Miller Fisher syndrome (MFS), a triad of ophthalmoplegia, areflexia and ataxia, is one of the regional variants of Guillain-Barré syndrome (GBS) that might account for a quarter of all cases of GBS, especially in Asian countries. There is history of an antecedent upper respiratory tract infection in up to two thirds of MFS cases. However, association of MFS in adults and pneumonia is rarely reported and in those cases causative pathogen was Mycoplasma pneumoniae. To our knowledge, association of MFS and ventilator-associated pneumonia has never been reported. So, we hereby report the first case of MFS which followed ventilator-associated pneumonia (VAP). Case Report: We report case of a 22-year-old male who was known to have temporal lobe epilepsy and mental retardation. He presented with status epilepticus. He was sedated and put on mechanical ventilation. Two days later, he developed a fever associated with increased tracheobronchial secretions and new infiltrates on chest X-ray. Diagnosis of VAP was made. Upon improvement, he was extubated and shifted out of ICU. Ten days after the onset of fever, he developed gradual onset bulbar weakness and ataxia. On examination, he had generalized areflexia and ataxia. CSF analysis showed cytoalbuminic dissociation. Antibodies against ganglioside complex were elevated. Diagnosis of sero-negative MFS was made, and intravenous immunoglobulin (IVIG) was started. He improved remarkably within two days. Conclusion: MFS is immune-mediated entity which is usually triggered by upper respiratory tract infection but in rare cases it can be consequence of pneumonia including VAP. Further research is needed to establish link between MFS and VAP.