Data-driven transcriptomics analysis identifies PCSK9 as a novel key regulator in liver aging.

The liver, as a crucial metabolic organ, undergoes significant pathological changes during the aging process, which can have a profound impact on overall health. To gain a comprehensive understanding of these alterations, we employed data-driven approaches, along with biochemical methods, histology, and immunohistochemistry techniques, to systematically investigate the effects of aging on the liver. Our study utilized a well-established rat aging model provided by the National Institute of Aging. Systems biology approaches were used to analyze genome-wide transcriptomics data from liver samples obtained from young (4-5 months old) and aging (20-21 months old) Fischer 344 rats. Our findings revealed pathological changes occurring in various essential biological processes in aging livers. These included mitochondrial dysfunction, increased oxidative/nitrative stress, decreased NAD + content, impaired amino acid and protein synthesis, heightened inflammation, disrupted lipid metabolism, enhanced apoptosis, senescence, and fibrosis. These results were validated using independent datasets from both human and rat aging studies. Furthermore, by employing co-expression network analysis, we identified novel driver genes responsible for liver aging, confirmed our findings in human aging subjects, and pointed out the cellular localization of the driver genes using single-cell RNA-sequencing human data. Our study led to the discovery and validation of a liver-specific gene, proprotein convertase subtilisin/kexin type 9 (PCSK9), as a potential therapeutic target for mitigating the pathological processes associated with aging in the liver. This finding envisions new possibilities for developing interventions aimed to improve liver health during the aging process.

Antidepressant Prescriptions in Neurosurgical Practice: A Survey of Current Trends.

AIM: To better understand the indications and the impact of antidepressant drugs on the field of neurosurgery in terms of risks and benefits in Turkey. MATERIAL AND METHODS: A national survey was conducted among neurosurgeons in current practice in Turkey to report routine prescription trends of antidepressant drugs. Gender, neurosurgical subspecialty, city, type of practice, years of experience, antidepressant agent, indications and reasons not to prescribe were ascertained. A brief review of literature was done to show clinical and research evidence. RESULTS: A total of 336 neurosurgeons took the survey; 53% of them prescribe antidepressants routinely, whereas 47% of them do not. Of the 72% non-prescribers prefer to refer their patients to a psychiatrist and 22% of them believe that antidepressants have no role in neurosurgery. Vascular and pediatric neurosurgeons as well as neurosurgeons at research hospitals showed the lowest prescription proportion, while general and brain tumor neurosurgeons and ones in private practice showed the highest prescription proportion. Surgeons with more than 20 year-experience had the lowest prescription proportion (43%). Type of practice and years of experience showed a statistically significant association with the prescription of antidepressant drugs across (p=0.002 and p=0.025, respectively). CONCLUSION: Type of practice and years of experience showed a statistically significant association with the proportion of antidepressants' prescribers in Turkish neurosurgery practice at the time of this survey. Non-prescriber neurosurgeons need to recognize the indications, whereas prescribers have to understand the risks of using antidepressants.

Proposal of a new radiological classification system for spinal meningiomas as a descriptive tool and surgical guide.

OBJECTIVES: 1) To provide neurosurgeons and radiologists with a new quantitative and anatomical method to describe spinal meningiomas (SM) consistently. 2) To provide a guide to the surgical approach needed and amount of bony resection required based on the proposed classification. 3) To report the distribution of our 58 cases of SM over different Stages and Subtypes in correlation to the surgical treatment needed for each case. 4) To briefly review the literature on the rare non-conventional surgical corridors to resect SM. PATIENTS AND METHODS: We reviewed the literature to report on previously published cohorts and classifications used to describe the location of the tumor inside the spinal canal. We reviewed the cases that were published prior showing non-conventional surgical approaches to resect spinal meningiomas. We proposed our classification system composed of Staging based on maximal cross-sectional surface area of tumor inside canal, Typing based on number of quadrants occupied by tumor and Subtyping based on location of the tumor bulk to spinal cord. Extradural and extra-spinal growth were also covered by our classification. We then applied it retrospectively on our 58 cases. RESULTS: 12 articles were published illustrating overlapping terms to describe spinal meningiomas. Another 7 articles were published reporting on 23 cases of anteriorly located spinal meningiomas treated with approaches other than laminectomies/laminoplasties. 4 Types, 9 Subtypes and 4 Stages were described in our Classification System. In our series of 58 patients, no midline anterior type was represented. Therefore, all our cases were treated by laminectomies or laminoplasties (with/without facetectomies) except a case with a paraspinal component where a costotransversectomy was needed. CONCLUSION: Spinal meningiomas can be radiologically described in a precise fashion. Selection of surgical corridor depends mainly on location of tumor bulk inside canal.