Endoscopic third ventriculostomy in the treatment of idiopathic normal pressure hydrocephalus: a review study

Idiopathic normal pressure hydrocephalus is a hydrodynamic disorder whose etiology remains unclear. The diagnosis is mainly clinical and the traditional treatment is cerebrospinal fluid shunt diversion. With the introduction of modern management strategies, endoscopic third ventriculostomy has become a viable alternative to shunting and constitutes a well-established method of treatment for obstructive hydrocephalus. The new hydrodynamic concept of hydrocephalus suggests that endoscopic third ventriculostomy (ETV) may be an effective treatment for communicative hydrocephalus. In our current review, the authors focus on the up-to-date knowledge regarding the consideration of endoscopic third ventriculostomy as a safe surgical option in the management of idiopathic normal pressure hydrocephalus.     

Sperm contributions to oocyte activation: more that meets the eye

It is well known that for successful fertilization, oocyte activation is required, which involves a signal transduction cascade leading to the conversion of the oocyte to a diploid embryo. During oocyte activation, intracellular calcium levels oscillate repetitively causing exocytosis of cortical granules, the enzymes which the latter contain are released into the perivitelline space, leading to modifications of the zona pellucida (ZP), which prevent the penetration of the ZP by further spermatozoa. Τhe necessary element that initiates oocyte activation is apparently the release of intracellular calcium (Ca²⁺) stored in the endoplasmic reticulum (ER). The exact mechanism via which Ca²⁺ is released within the oocyte has not been yet clarified, and has been a matter of an ongoing debate. Today, the sperm factor hypothesis has gained general acceptance, according to which a sperm molecule, either phospholipase C (PLCζ) or a post-acrosomal sheath WW domain-binding protein (PAWP), diffuses into the ooplasm initiating a molecular cascade involving mainly the phosphoinositide pathway. Mounting evidence now indicates that these calcium oscillations are caused by a testis-specific PLC termed PLCζ, released into the oocyte following gamete fusion. Also, recently, PAWP has been proposed as an alternative sperm factor candidate. These different sperm candidates have led to a significant debate. This raises important questions as regards to the relative importance of these two proteins as diagnostic tools in reproductive medicine with therapeutic potential, indicating the need for further research. In the present mini review, the phenomenon of oocyte activation during fertilization as well as the existing controversy will be highlighted and the possible mechanisms that are involved in this process will be discussed. Finally, an explanation of the existing debate will be attempted.     

Biomarkers in sarcoidosis

Introduction: Numerous biomarkers have been evaluated for the diagnosis, assessment of disease activity, prognosis, and response to treatment in sarcoidosis. In this report, we discuss the clinical and research utility of several biomarkers used to evaluate sarcoidosis.

Areas covered: The sarcoidosis biomarkers discussed include serologic tests, imaging studies, identification of inflammatory cells and genetic analyses. Literature was obtained from medical databases including PubMed and Web of Science.

Expert commentary: Most of the biomarkers examined in sarcoidosis are not adequately specific or sensitive to be used in isolation to make clinical decisions. However, several sarcoidosis biomarkers have an important role in the clinical management of sarcoidosis when they are coupled with clinical data including the results of other biomarkers.     

Profiling of drugs and environmental chemicals for functional impairment of neural crest migration in a novel stem cell-based test battery

Developmental toxicity in vitro assays have hitherto been established as stand-alone systems, based on a limited number of toxicants. Within the embryonic stem cell-based novel alternative tests project, we developed a test battery framework that allows inclusion of any developmental toxicity assay and that explores the responses of such test systems to a wide range of drug-like compounds. We selected 28 compounds, including several biologics (e.g., erythropoietin), classical pharmaceuticals (e.g., roflumilast) and also six environmental toxicants. The chemical, toxicological and clinical data of this screen library were compiled. In order to determine a non-cytotoxic concentration range, cytotoxicity data were obtained for all compounds from HEK293 cells and from murine embryonic stem cells. Moreover, an estimate of relevant exposures was provided by literature data mining. To evaluate feasibility of the suggested test framework, we selected a well-characterized assay that evaluates ‘migration inhibition of neural crest cells.’ Screening at the highest non-cytotoxic concentration resulted in 11 hits (e.g., geldanamycin, abiraterone, gefitinib, chlorpromazine, cyproconazole, arsenite). These were confirmed in concentration–response studies. Subsequent pharmacokinetic modeling indicated that triadimefon exerted its effects at concentrations relevant to the in vivo situation, and also interferon-β and polybrominated diphenyl ether showed effects within the same order of magnitude of concentrations that may be reached in humans. In conclusion, the test battery framework can identify compounds that disturb processes relevant for human development and therefore may represent developmental toxicants. The open structure of the strategy allows rich information to be generated on both the underlying library, and on any contributing assay.     

Focus on HPV Infection and the Molecular Mechanisms of Oral Carcinogenesis

This study is focused on the epidemiological characteristics and biomolecular mechanisms that lead to the development of precancerous and cancerous conditions of oral lesions related to Human Papilloma Virus (HPV) infections. Current evidence from the literature demonstrates the role of HPV in potentially malignant oral disorders. Therefore, the underlying biomolecular processes can give arise, or contribute to, benign lesions as well as to oral carcinogenesis.     

Predictors and Outcomes of Renal Replacement Therapy After Left Ventricular Assist Device Implantation

ObjectiveTo examine the frequency and outcomes of patients requiring renal replacement therapy (RRT) early after left ventricular assist device (LVAD) implantation.Patients and MethodsWe examined use of in-hospital RRT and outcomes in consecutive adults who underwent continuous-flow LVAD implantation from February 15, 2007, through August 8, 2017. Logistic regression was used to examine predictors of RRT. The associations of RRT with outcomes were examined using Cox proportional hazards regression.ResultsOf 354 patients who underwent LVAD implantation, 54 (15%) required in-hospital RRT. Patients receiving RRT had higher preoperative Charlson Comorbidity Index values (median, 5 vs 4; P=.03), Model for End-Stage Liver Disease scores (mean, 19.0 vs 14.5; P<.001), right atrial pressure (mean, 19.1 vs 13.4 mm Hg; P<.001), and estimated 24-hour urine protein levels (median, 357 vs 174 mg; P<.001) and lower preoperative estimated glomerular filtration rate (eGFR) (median, 43 vs 57 mL/min; P<.001) and measured GFR using ¹²⁵I-iothalamate clearance (median, 33 vs 51 mL/min; P=.001) than those who did not require RRT. Approximately 40% of patients with eGFR less than 45 mL/min/1.73 m² and 24-hour urine protein level greater than 400 mg required RRT vs 6% with eGFR greater than45 mL/min/1.73 m² and without significant proteinuria. Lower preoperative eGFR, higher estimated 24-hour urine protein level, higher right atrial pressure, and longer cardiopulmonary bypass time were independent predictors of RRT after LVAD implantation. Of patients requiring in-hospital RRT, 18 (33%) had renal recovery, 18 (33%) required outpatient hemodialysis, and 18 (33%) died before hospital discharge. After median (Q1, Q3) follow-up of 24.3 (8.9, 49.6) months, RRT was associated with increased risk of death (adjusted hazard ratio [HR], 2.86; 95% CI, 1.90-4.33; P<.001) and gastrointestinal bleeding (adjusted HR, 4.47; 95% CI, 2.57-7.75; P<.001).ConclusionIn-hospital RRT is associated with poor prognosis after LVAD. A detailed preoperative assessment of renal function before LVAD may be helpful in risk stratification and patient selection.