Screening of Three Echinoderm Species as New Opportunity for Drug Discovery: Their Bioactivities and Antimicrobial Properties

Echinoderms are a renewable resource with an economic value due to their increasing demand as food and/or source of bioactive molecules exerting antitumor, antiviral, anticoagulant, antioxidant, and antimicrobial activities. In this framework, the present study is aimed at investigating the antibacterial, antioxidant, and hemolytic activities in the three Echinoderm species Echinaster sepositus, Arbacia lixula, and Sphaerechinus granularis. The sea star E. sepositus showed lysozyme-like activity (mean diameter of lysis of 13.4±0.2 mm), an antimicrobial activity against the human emerging pathogens Staphylococcus aureus, Pseudomonas aeruginosa, and Candida famata, and a strong lytic activity (100±0.05%) towards the human red blood cells. Furthermore A. lixula and E. sepositus had the highest antioxidant activity (1792.75±233.7 and 1765.65±484.58 nmolTE/mL, resp.). From toxicological assays, it was shown that E. sepositus was not toxic towards HeLa cells and Vibrio fischeri, encouraging the exploitation of this species in the pharmaceutical field. Therefore, our findings have implications due to the ongoing explosion of antibiotic-resistant infections because of the new opportunistic pathogens and the need to discover antibacterial agents with new modes of action. Also the recorded antioxidant activity taking into account the need to find natural antioxidants useful for human health is intriguing

Detailed knowledge of regional anatomy and anatomical variations is fundamental to achieve successful surgical procedure. Although primary objective of neurosurgery is to restore physiological vital functions, remove intracranial mass and prevent further

Detailed knowledge of regional anatomy and anatomical variations is fundamental to achieve successful surgical procedure. Although primary objective of neurosurgery is to restore physiological vital functions, remove intracranial mass and prevent further brain damage, while preserving tissue and organ integrity, the neurosurgeon takes the risk of impairing non-vital functions. Occasionally, as with the hypoglossal nerve, the impairment of anatomical structures found on surgical route is due to their still barely known anatomical relations and variations. In order to provide an anatomically and surgically oriented classification to guide neurosurgical procedures and to ensure the preservation of nerve integrity, the aim of the present study is to detail the course of the 12th cranial nerve (CN) and to establish anatomical landmarks for surgeons. A combination of anatomical dissection of the neck and oral floor and skull base far lateral approach of 6 cadaveric human heads (3 male, 3 female, age 62+4) was performed, on both sides, to explore and follow the entire course of the 12th CN, from its emergence in the preolivary sulcus to the tongue. Skeletal, muscular and vascular relationships were meticulously analyzed and documented during anatomic and surgical dissections. According to our observations, hypoglossal nerve can be divided into five segments. The first two are intracranial, cisternal and intracanalar, and the other three, namely the descending, horizontal and ascending, are extracranial. Intriguingly, we found unreported relations of the nerve that, apart from their anatomical interest, have tremendous significance for surgeons operating on head and neck. Specifically, the intracanalar segment passes through a venous lacuna that, to the best of our knowledge, was never described before as such. This venous structure drains into the jugular bulb and acts as a sheath between the nerve and the osseous wall of the canal. The nerve in the venous sheath bends and it is elastically fixed to the osseous wall of the canal by fibrous bands. Therefore, the venous lacuna guarantees mobility to the nerve, and cushion the nerve from the bone. As for the descending segment, during its course it has very close relationship with the internal jugular vein, the internal carotid artery, the posterior belly of digastric muscle, and the styloid process and muscles inserting on it. The descending segment provides the ansa hypoglossi, branches to muscles inserting on the styloid process and to the sternocleidomastoid muscle. The horizontal segment has relationship with the intermediate digastric tendon, the stylohyoid, hyoglossus and mylohyoid muscles and the submandibular gland. The ascending segment might be very short and sometimes it is absent. The fifth and last segment becomes deeper at the anterior edge of hyoglossus muscle, and terminates into several branches supplying intrinsic and extrinsic musculature of tongue

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

The Hypoglossal Nerve: Anatomical Study of Its Entire Course

Objective Only a few anatomic studies of the entire course of the hypoglossal nerve (cranial nerve XII) have been reported. We analyzed all relationships of the 12th nerve with surrounding structures from the brainstem to the tongue through a microscopic perspective. A comprehensive anatomically and clinically oriented classification of its different segments is proposed. Methods Ten formalin-fixed adult human cadaveric heads (20 sides) were dissected with the aim to explore the entire course of cranial nerve XII via lateral suboccipital, far lateral partial, or total transcondylar routes. Different segments of the nerve were identified based on the hypoglossal course and its relationship with surrounding structures. Measurements of every portion of the nerve were taken in all specimens during dissection. Results The hypoglossal nerve was divided into 5 segments: cisternal, intracanalar, descending, horizontal, and ascending. Detailed and comprehensive examination of basic anatomic relationships through the view of different transcranial and endoscope-assisted approaches was performed. A new perspective of the hypoglossal canal is proposed, and the venous plexus surrounding the intracanalar segment of the nerve is described in detail. Conclusions Classification of 5 segments for the hypoglossal nerve seems anatomically valid, and it is surgically oriented with respect to all surgical approaches. Precise knowledge of the relationships with the surrounding structures may help to prevent some complications during surgery, and it is useful to explain, segment by segment, the pathogenic mechanisms for nerve injuries that are evidenced by lesions that exist along the entire intracranial and extracranial course

Defining the lateral limits of the endoscopic endonasal transtuberculum transplanum approach: anatomical study with pertinent quantitative analysis

OBJECTIVE The extended endoscopic endonasal transtuberculum transplanum approach is currently used for the surgical treatment of selected midline anterior skull base lesions. Nevertheless, the possibility of accessing the lateral aspects of the planum sphenoidale could represent a limitation for such an approach. To the authors' knowledge, a clear definition of the eventual anatomical boundaries has not been delineated. Hence, the present study aimed to detail and quantify the maximum amount of bone removal over the planum sphenoidale required via the endonasal pathway to achieve the most lateral extension of such a corridor and to evaluate the relative surgical freedom. METHODS Six human cadaveric heads were dissected at the Laboratory of Surgical NeuroAnatomy of the University of Barcelona. The laboratory rehearsals were run as follows: 1) preliminary predissection CT scans, 2) the endoscopic endonasal transtuberculum transplanum approach (lateral limit: medial optocarotid recess) followed by postdissection CT scans, 3) maximum lateral extension of the transtuberculum transplanum approach followed by postdissection CT scans, and 4) bone removal and surgical freedom analysis (a nonpaired Student t-test). A conventional subfrontal bilateral approach was used to evaluate, from above, the bone removal from the planum sphenoidale and the lateral limit of the endonasal route. RESULTS The endoscopic endonasal transtuberculum transplanum approach was extended at its maximum lateral aspect in the lateral portion of the anterior skull base, removing the bone above the optic prominence, that is, the medial portion of the lesser sphenoid wing, including the anterior clinoid process. As expected, a greater bone removal volume was obtained compared with the approach when bone removal is limited to the medial optocarotid recess (average 533.45 vs 296.07 mm2; p < 0.01). The anteroposterior diameter was an average of 8.1 vs 15.78 mm, and the laterolateral diameter was an average of 18.77 vs 44.54 mm (p < 0.01). The neurovascular contents of this area were exposed up to the insular segment of the middle cerebral artery. The surgical freedom analysis revealed a possible increased lateral maneuverability of instruments inserted in the contralateral nostril compared with a midline target (average 384.11 vs 235.31 mm2; p < 0.05). CONCLUSIONS Bone removal from the medial aspect of the lesser sphenoid wing, including the anterior clinoid process, may increase the exposure and surgical freedom of the extended endoscopic endonasal transtuberculum transplanum approach over the lateral segment of the anterior skull base. Although this study represents a preliminary anatomical investigation, it could be useful to refine the indications and limitations of the endoscopic endonasal corridor for the surgical management of skull base lesions involving the lateral portion of the planum sphenoidale

Surgical Back Risk Syndrome and Spinal Cord Stimulation: Better Safe Than Sorry

Background: Recurrent and chronic low back pain, caused by degenerative lumbar spondylosis, commonly affects elderly patients, even those with no previous low back surgery. These patients, like those affected by failed back surgery syndrome (FBSS), may become unresponsive to medical conservative treatment and their quality of life could be easily compromised. Moreover, general comorbidities, obesity, and other typical conditions of the elderly may make surgery under general anesthesia riskier than the natural history of the disease. These patients could be considered affected by surgical back risk syndrome (SBRS). Methods: In this article, we report our preliminary observational prospective study on the role of spinal cord stimulation (SCS) in 3 groups of patients: the FBSS group, the SBRS group, and the "other" group. Selection criteria, treatment modality, and outcomes for each patient group are described and discussed. Moreover, a potentially useful diagnostic and therapeutic flowchart on the management options for lumbar back diseases is discussed. Results: The FBSS group included 25 patients, the SBRS group included 10 patients, and the other group included 3 patients. In 22/25 patients with FBSS (88% of the total), the implantation of a definitive neurostimulator was successful. In almost all patients in both the SBRS and the other groups, the implantation of a definitive neurostimulator was successful. Conclusions: In our opinion, SCS could be considered as a valid alternative treatment not only in selected patients affected by FBSS but also in selected patients affected by SBRS, in whom back surgery under general anesthesia may be challenging and overcome the potential benefit of the surgery itself. SBRS could be considered a new disease entity to be managed through SCS