Rational modification of estrogen receptor by combination of computational and experimental analysis

In this manuscript, we modulate the binding properties of estrogen receptor protein by rationally modifying the amino acid composition of its ligand binding domain. By combining sequence alignment and structural analysis of known ER-ligand complexes with computational analysis, we were able to predict ER mutants with altered binding properties. These predictions were experimentally confirmed by producing single point variants with up to an order of magnitude increased binding affinity towards some estrogen disrupting chemicals and reaching an IC50 value of 2 nM for the 17α−Ethinylestradiol ligand. Due to increased affinity and stability, utilizing such mutated ERs instead of the wild type ER as bio-recognition element would be beneficial in an assay or biosensor.JRC.I-Institute for Health and Consumer Protection (Ispra

Idatidosi Splenica. Descrizione di un caso clinico e revisione della letteratura

A rare case of primary hydatid cyst of the spleen is described. The hypotheses of this possible primary localization, diagnostic techniques and the therapeutic management are discussed

Clinical Significance of Hypokalemia in Blunt Liver Trauma: Preliminary Findings in a Retrospective Cohort Study of 164 Patients

Background: The clinical significance of serum potassium levels at admission in patients with blunt hepatic trauma remains insufficiently defined. This study aimed to evaluate the prevalence and prognostic value of admission hypokalemia in this patient population. Methods: We conducted a retrospective analysis of 164 patients with radiologically confirmed blunt liver trauma admitted between 2016 and 2023. Preoperative, intraoperative, and postoperative data were collected to assess the association between serum potassium levels and trauma severity (AAST grade—American Association for the Surgery of Trauma, ISS—Injury Severity Score), in-hospital morbidity, mortality, and length of stay. Univariate and multivariate analyses were performed, including checks for normality and multicollinearity. Results: Serum potassium levels showed a significant positive correlation with age (p = 0.0064), and an inverse correlation with liver injury severity (AAST grade; p = 0.01). Lower potassium levels were associated with longer hospital stays (p = 0.0459) and higher morbidity (p = 0.022). In multivariate analysis, only age (p = 0.036) and AAST grade (p = 0.014) were independent predictors of serum potassium concentration. Potassium levels were not independently associated with mortality. Conclusions: Admission hypokalemia is a common finding in blunt liver trauma and correlates with injury severity and adverse clinical outcomes. Potassium concentration may serve as a readily available, low-cost biomarker for early risk stratification in these patients. Further prospective studies are warranted to confirm its prognostic utility

Rational engineering of a human anti-dengue antibody through experimentally validated computational docking

Antibodies play an increasing pivotal role in both basic research and the biopharmaceutical sector, therefore technology for characterizing and improving their properties through rational engineering is desirable. This is a difficult task thought to require high-resolution x-ray structures, which are not always available. We, instead, use a combination of solution NMR epitope mapping and computational docking to investigate the structure of a human antibody in complex with the four Dengue virus serotypes. Analysis of the resulting models allows us to design several antibody mutants altering its properties in a predictable manner, changing its binding selectivity and ultimately improving its ability to neutralize the virus by up to 40 fold. The successful rational design of antibody mutants is a testament to the accuracy achievable by combining experimental NMR epitope mapping with computational docking and to the possibility of applying it to study antibody/pathogen interactions

Importanza di una diagnosi precoce per un corretto trattamento chirurgico della PAES (Sindrome da intrapolamento dell’arteria poplitea).

Popliteal artery entrapment syndrome (PAES) is an uncommon pathological entity, caused by segmental popliteal artery compression by the surrounding myofascial structures. Clinical symptoms may appear acutely, with temporary ischaemic attacks, or chronically, with concerned calf claudicatio intermittens and for 30% are bilateral. Diagnosis, besides being based on clinical objectivity (acute and deep pain to the struck limb, mainly during active plantar hyperextension) and history-taking (subject-age and lack of atherosclerosis), is based on ultrasonographic (eco-color Doppler of the aortic-iliac-femural-popliteal trunks, tensiometric Doppler), angio-RM, angio-CT scan and dynamic angiographic exams. Treatment, essentially, is surgical by simple freeing of the popliteal artery from surrounding myofascial structures or by autologous vein (saphenous v.) interposition grafting and patching, or bypass without vessel resection. About clinical case reported by the authors, 44-years female with left calf acute pain symptoms, cold skin by the thermo-touch, hypo-paraesthesia with fifth toe cyanosis and walking inability, surgical treatment, because of precox diagnosis, consisted of simple cut of myofibrous shoot starting from medial head of the left gastrocnemious muscle and compressing popliteal artery, with clinical chart complete resolution

Rational modification of estrogen receptor by combination of computational and experimental analysis

In this manuscript, we modulate the binding properties of estrogen receptor protein by rationally modifying the amino acid composition of its ligand binding domain. By combining sequence alignment and structural analysis of known estrogen receptor- ligand complexes with computational analysis, we were able to predict estrogen receptor mutants with altered binding properties. These predictions were experimentally confirmed by producing single point variants with up to an order of magnitude increased binding affinity towards some estrogen disrupting chemicals and reaching an half maximal inhibitory concentration (IC50) value of 2 nM for the 17α- ethinylestradiol ligand. Due to increased affinity and stability, utilizing such mutated estrogen receptor instead of the wild type as bio-recognition element would be beneficial in an assay or biosensor

Vitreous Substitutes: The Present and the Future

Vitreoretinal surgery has advanced in numerous directions during recent years. The removal of the vitreous body is one of the main characteristics of this surgical procedure. Several molecules have been tested in the past to fill the vitreous cavity and to mimic its functions. We here review the currently available vitreous substitutes, focusing on their molecular properties and functions, together with their adverse effects. Afterwards we describe the characteristics of the ideal vitreous substitute. The challenges facing every ophthalmology researcher are to reach a long-term intraocular permanence of vitreous substitute with total inertness of the molecule injected and the control of inflammatory reactions. We report new polymers with gelification characteristics and smart hydrogels representing the future of vitreoretinal surgery. Finally, we describe the current studies on vitreous regeneration and cell cultures to create new intraocular gels with optimal biocompatibility and rheological properties

Classification tree to analyze factors connected with post operative complications of cataract surgery in a teaching hospital

Background: Artificial intelligence (AI) is becoming ever more frequently applied in medicine and, consequently, also in ophthalmology to improve both the quality of work for physicians and the quality of care for patients. The aim of this study is to use AI, in particular classification tree, for the evaluation of both ocular and systemic features involved in the onset of complications due to cataract surgery in a teaching hospital. Methods: The charts of 1392 eyes of 1392 patients, with a mean age of 71.3 8.2 years old, were reviewed to collect the ocular and systemic data before, during and after cataract surgery, including post-operative complications. All these data were processed by a classification tree algorithm, producing more than 260 million simulations, aiming to develop a predictive model. Results: Postoperative complications were observed in 168 patients. According to the AI analysis, the pre-operative characteristics involved in the insurgence of complications were: ocular comorbidities, lower visual acuity, higher astigmatism and intra-operative complications. Conclusions: Artificial intelligence application may be an interesting tool in the physician’s hands to develop customized algorithms that can, in advance, define the post-operative complication risk. This may help in improving both the quality and the outcomes of the surgery as well as in preventing patient dissatisfaction