Laboratory criteria of perinatal damage of central nervous system at premature newborns

Introduction: Fetal and neonatal hypoxia takes a special place among the damaging factors of central nervous system (CNS). All forms of oxygen deficiency are accompanied by the development of bioenergetic hypoxia, which leads to tension of metabolic processes of the organism. Metabolic effect of hypoxia includes stark reduce of mitochondrial activity due to a significant inhibition enzymes of the Krebs cycle: succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH). In newborn babies is not always possible to objectively assess the condition of the CNS defeat, because very often the severity of lesions does not correspond to clinical symptoms, especially in premature newborns. So far determination the severity of hypoxic-ischemic CNS lesions is still very actual in modern medicine. More objective method of such an assessment is determine the activity of neurospecific enolase (NSE). The aim of the paper is to increase the efficiency of diagnosis of hypoxic CNS lesions in premature infants by determining the activity of NSE and study energy supply during the neonatal period. Material and methods: The concentration of NSE, SDH and LDH were determined in 15 conventionally healthy preterm infants (CHPI), which made the comparison group, and 64 premature babies with hypoxic-ischemic CNS lesions, which were divided into three groups: I group ­ 26 premature children with mild CNS lesions; II group ­ 20 premature children with severe hypoxic lesions and low birth weight; III group ­ 18 premature newborns with severe damage of central nervous system and extremely low birth weight. NSE activity was determined by enzyme immunoassay using reagents of the company «Fujirebio¼ (Sweden) on an automatic analyzer «Multiscan Plus¼ company «Labsystems¼ (Finland). Material for investigation was peripheral venous blood of newborns, which collected by vein punction at morning on an empty stomach. Results and conclusions: Metabolic effect of hypoxia in premature infants manifested by severe inhibition of mitochondrial respiratory activity, which appears in the reduction of aerobic enzyme activity of SDH and activation serum LDH. During the neonatal period in infants with perinatal hypoxic- ischemic lesions of the CNS levels of the of NSE, SDH and LDG aren't normalized, that indicated on energy deficiency and requires the development of effective methods of correcting this condition. Perinatal hypoxia in premature neonates causes significant alteration of neuronal membranes and increase concentration in blood such neurospecific protein as NSE, whose concentration correlates with the degree of severity of CNS injury.

Conjunctional Concepts: The Conceptual Teaching Technique in Biology Classes.

Conceptual teaching relies on concepts in conjunction with a bigger conceptual category (or categories). Revealing and using conceptual conjunctions in the science classroom means teaching conceptually. To make conceptual teaching more accessible to biology instructors, a three-concept model was described to be used during a lecture. This model has allowed the author to develop a relatively simple method that starts with an active concept or concepts, then introduces conjunctional and supporting concepts to relate the content to other concepts and relevant real-world applications. This method is intended to help instructors in preparing to teach biological concepts conceptually, in order to foster an enduring understanding of biological principles in their students.

Overall survival in patients with metastatic renal cell carcinoma in Russia, Kazakhstan, and Belarus: a report from the RENSUR3 registry.

BACKGROUND: Real-world data describing outcomes of treatment among metastatic renal cell carcinoma (mRCC) patients are limited and heterogeneous. AIM: RENSUR3 registry study assessed real-world data on the use of therapies in mRCC and overall survival (OS) in Russia, Kazakhstan, and Belarus. METHODS: Patients were included in the retrospective multicenter registry study. To be eligible, patients were required to have mRCC diagnosed from January 2015 to January 2016. Anonymized data were collected through an online registry. The outcomes of interest were patient characteristics, treatment patterns, and OS. RESULTS: 1094 mRCC patients were identified. Mean age was 62.3 (SD, 11.2) years. Four hundred and forty-four (41%) patients were 65 years and older. Primary tumor has not been removed in 503 (46%) patients. Subtype of RCC based on WHO classification (clear-cell or other) has been reported in 402 (37%) patients. In total, 595 (54.4%) patients received systemic therapy for metastatic disease. 58% of elderly patients (≥65) were not treated compared to 37% of younger patients. Cytokines and targeted therapy were used in 298 (50.1%) and 297 (49.9%) of 595 treated patients, respectively. Median OS was 11.9 months (95% CI 10.9-12.9). The 1- and 3-year OS rates were 49.6% and 19.3%. CONCLUSIONS: Half of patients received no systemic therapy or had only cytokines for mRCC in Russia, Kazakhstan, and Belarus, which doubtless negatively affected OS in this population. Novel therapies should be considered as life prolonging and a priority.

Five-year Survival of Patients With Metastatic Renal Cell Carcinoma in the Russian Federation: Results From the RENSUR5 Registry.

BACKGROUND: The 5-year overall survival (OS) of patients with metastatic renal cell carcinoma (mRCC) has been rarely reported. The aim of the RENSUR5 registry study was to obtain real-world data on the use of therapy for mRCC and assess the 5-year OS in the Russian population. PATIENT AND METHODS: Patients were retrospectively identified at 11 cancer centers in different regions of Russia (Astrakhan, Barnaul, Ekaterinburg, Kazan, Krasnoyarsk, Obninsk, Omsk, Rostov-on-Don, Samara, St. Petersburg, and Ufa). Patients were included if mRCC had been diagnosed from January 2010 to January 2011. Anonymized data were collected through an online registry covering the demographic data, treatments, and outcomes. RESULTS: A total of 439 adult mRCC patients were included in the present study for analysis. The mean age at diagnosis of mRCC was 60.9 years (range, 33-90 years; with 9% of patients aged ≥ 75 years). The patients were predominantly men (70.2%) and 67.7% had nephrectomy. Clear cell and non-clear cell tumors were detected in 61.1% and 7.7% of patients, respectively. A total of 271 patients (62%) received systemic therapy. The median duration of therapy was 11 months (95% confidence interval, 9.5-12.5 months). Most treatment was with interferon only (n = 145); 105 patients (23.9%) received targeted therapy, and 69 patients (15.7%) received ≥ 2 treatment lines. The 1-, 3-, and 5-year OS rate was 49.4%, 18.9%, and 8.2%, respectively. The median OS from the start of treatment was 12 months (95% confidence interval, 9.7-14.4 months). CONCLUSION: RENSUR5 is a large real-world database assessing the mRCC treatment patterns and 5-year OS in Russia. According to the first results of the present study, we believe that 5-year OS should improve with novel therapies. The limited administration of targeted therapies was reflected by the results of the 5-year survival rate. The treatment of mRCC has changed in the past years with new treatment options significantly improving OS. The 5-year OS of patients treated with immunotherapy and targeted therapy should be analyzed in the real world.

The prion dilemma confounding science educators.

In this paper, the issue of the prion hypothesis, a simmering controversy within the scientific community, is addressed. We inquire into the appropriateness of the use of certain augmentations and rhetoric approaches used during scientific debates, as well as the aptness of unequivocal statements in textbooks that indicate "abnormal prions" as a primary cause of Transmissible Spongiform Encephalopathies.

Biweekly docetaxel is better tolerated than conventional three-weekly dosing for advanced hormone-refractory prostate cancer.

BACKGROUND: Docetaxel administered every three weeks is the standard treatment for advanced hormone-refractory prostate cancer (HRPC). However, biweekly administration might be better tolerated due to the reduced peak drug concentrations. Therefore, we compared biweekly to triweekly docetaxel as first- or second-line chemotherapy for advanced HRPC in this prospective randomized multicenter trial. PATIENTS AND METHODS: In this study, 360 patients were randomly allocated to receive docetaxel 75 mg/m(2) i.v. d1 q3 weeks (tT) or 50 mg/m(2) i.v. d1 and d 14, q4 weeks (bT) from March 2004 to May 2009. Oral prednisolone (10 mg/day) was administered in both groups. The groups were well balanced according to the WHO performance status in terms of mean age (70 vs. 68, range 45-87 years) and median serum PSA level at the time of study entry (109 vs. 98 µg/l, range 11-1490 µg/l). The primary endpoint was time to treatment failure (TTF). ClinicalTrials.gov study identifier: NCT00255606. RESULTS: Ultimately, 158 patients (tT=79; bT=79) were included in this preplanned interim safety analysis; 567 and 487 cycles (equivalent to 1701 and 1948 weeks of treatment) were administered in the tT and bT groups, respectively. The most common grade 3-4 adverse events (expressed as %/cycles) in tT /bT were neutropenia 20%/14%; infection with/without neutropenia 8%/3%; fatigue 3%/3%; febrile neutropenia 2%/1%; and bone pain 2%/1%. Serious adverse events occurred more frequently in the group tT (n=60, 10.6% of cycles) than in the group bT (n=29, 6.0%, p=0.012). One patient died due to coronary infarction, and another was diagnosed with acute lymphocytic leukemia (both in the bT group). Thirty patients (38%) in the bT group and 22 patients (28%) in the tT group were still receiving treatment at 6 months (p=0.176). CONCLUSION: Biweekly docetaxel was tolerated better than conventional triweekly with fewer serious adverse events and more patients were still on the therapy at 6 months. Biweekly docetaxel therapy might be considered as an option for elderly patients exhibiting a compromised general condition.