Comparative assessment of methods of the operative treatment of facial nerve damage caused during cerebellopontine angle neurinoma and meningioma removals

The aim of this research paper is to point out the preconditions for facial nerve damage during CPA tumour removals and, in such cases, the appropriate choice of reconstructive surgery. Materials and methods. In Uzhhorod National University, during the period of 2008 to 2019, surgical treatment of 212 patients with neurinomas and meningiomas of the CPA has been carried out. We have analyzed the cases of 35 (16.5%) patients with intraoperative damage of the facial nerve. The mentioned 35 patients underwent appropriate clinical examinations during the post-operative period, which confirmed the facial nerve damage to one degree or another according to the House-Brackmann scale. The clinical signs manifested as full eyelid contact with slight effort and slight facial asymmetry during maximal effortful laughter. Slight synkinesias were noticeable, and there were no contractures until the expression of clinical signs corresponding to grade 6 - total nerve paralysis in 5 patients. Results. The research demonstrated that patients with neurinomas larger than 3 cm in size are 5 times more likely to undergo intraoperative damage to the facial nerve than patients with the same tumour but 3 cm or less in size and 5 times more likely than patients with meningiomas as a whole. In the group of patients aged 20-40, there were twice as many men; in the group aged 40-50, women predominated; among patients older than 50, there were equal numbers of men and women. Remote catamnesis was traced in 19 patients, and contact with the rest of the patients was lost due to the war. Among the interviewed patients, 58% of the anastomosis was performed in the first 3 months after the initial surgery, 21% - in 4-6 months, and 21% - in more than 12 months. The optimal timing of reinnervation after the initial surgery is the first 6 months after tumour removal. Сonclusions. Nerve damage is more common during the removal of neurinomas 4cm or bigger in size. Reinnervation is accomplished by anastomosing the central end of the hypoglossal or accessory nerves to the peripheral end of the facial nerve, and both procedures are equally effective. Reinnervation should be performed 2 to 3 months after confirming nerve injury, but no later than 6 months

PCB 126 and Other Dioxin-Like PCBs Specifically Suppress Hepatic PEPCK Expression via the Aryl Hydrocarbon Receptor

Dioxins and dioxin-like compounds encompass a group of structurally related heterocyclic compounds that bind to and activate the aryl hydrocarbon receptor (AhR). The prototypical dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic industrial byproduct that incites numerous adverse physiological effects. Global commercial production of the structurally similar polychlorinated biphenyls (PCBs), however, commenced early in the 20th century and continued for decades; dioxin-like PCBs therefore contribute significantly to total dioxin-associated toxicity. In this study, PCB 126, the most potent dioxin-like PCB, was evaluated with respect to its direct effects on hepatic glucose metabolism using primary mouse hepatocytes. Overnight treatment with PCB 126 reduced hepatic glycogen stores in a dose-dependent manner. Additionally, PCB 126 suppressed forskolin-stimulated gluconeogenesis from lactate. These effects were independent of acute toxicity, as PCB 126 did not increase lactate dehydrogenase release nor affect lipid metabolism or total intracellular ATP. Interestingly, provision of cells with glycerol instead of lactate as the carbon source completely restored hepatic glucose production, indicating specific impairment in the distal arm of gluconeogenesis. In concordance with this finding, PCB 126 blunted the forskolin-stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels without affecting glucose-6-phosphatase expression. Myricetin, a putative competitive AhR antagonist, reversed the suppression of PEPCK induction by PCB 126. Furthermore, other dioxin-like PCBs demonstrated similar effects on PEPCK expression in parallel with their ability to activate AhR. It therefore appears that AhR activation mediates the suppression of PEPCK expression by dioxin-like PCBs, suggesting a role for these pollutants as disruptors of energy metabolism

Structure-based vaccine design by electron microscopy

Modern vaccine design relies on multiscale, interdisciplinary efforts that take advantage of innovative technologies such as in silico identification of antigens, high throughput screening of antigen immunogenicity, and gene expression profiling to predict host immune responses. In recent years, structural analysis has played an increasingly important role in vaccine development as a means to improve antigen stability, immunogenicity and large scale production. Transmission electron microscopy (TEM), and in particular cryo-TEM, is an established and powerful imaging technique applicable to many specimens, including the three-dimensional (3D) reconstruction of macromolecules and their associated complexes to high resolution. The technique is parsimonious in its material requirements and captures the specimens in their fully hydrated state, close to their native environment. The resolution of cryo-TEM reconstructions was limited to the subnanometer range until the recent development of direct electron detectors and improvements in image processing software, which has led to a so-called “resolution revolution” in the cryo-TEM field. Several protein structures have now been solved at near atomic resolution, establishing the technique as a viable alternative to X-ray analysis for high resolution structure determination. We have determined several structures with and without bound compounds at 2.9 Å – 3.6 Å resolution, which are being integrated into drug discovery and development workflows by our clients. Here we present the 2.4Å resolution structure of apoferritin determined with our Titan Krios electron microscope as an example of the cryo-TEM services available at NIS. These services are significantly enhanced with unique access by NIS to a new instrument, Spotiton, a robotic device that dispenses picoliter-volumes of sample onto a self-blotting nanowire grid as it flies past en route to vitrification. This provides several advantages over standard vitrification methods, including more automated and reproducible preparation of specimens and reducing the deleterious effects of particles interacting with the air-water interface. While high resolution 3D structure determination by cryo-TEM is at the forefront of structural biology, averages of 2D projection images at moderate resolution in negative stain or vitreous ice can also provide a wealth of information that may be difficult to obtain using other methods. This is illustrated in a number of case studies, including (1) mapping of neutralizing epitopes on the CMV pentameric glycoprotein complex; (2) mapping of neutralizing epitopes on the HIV-1 envelope glycoprotein trimer; (3) assessment of structure and conformational stability of pre- and post-fusion RSV-F protein; (4) characterization of novel adjuvants and protein delivery systems. In summary, both the moderate resolution TEM and high resolution cryo-TEM methods are well suited to extensively characterize antigen structure-function relationships, some of which may be refractory to other experimental methods

Metabolism disrupting chemicals and metabolic disorders

The recent epidemics of metabolic diseases, obesity, type 2 diabetes(T2D), liver lipid disorders and metabolic syndrome have largely been attributed to genetic background and changes in diet, exercise and aging. However, there is now considerable evidence that other environmental factors may contribute to the rapid increase in the incidence of these metabolic diseases. This review will examine changes to the incidence of obesity, T2D and non-alcoholic fatty liver disease (NAFLD), the contribution of genetics to these disorders and describe the role of the endocrine system in these metabolic disorders. It will then specifically focus on the role of endocrine disrupting chemicals (EDCs) in the etiology of obesity, T2D and NAFLD while finally integrating the information on EDCs on multiple metabolic disorders that could lead to metabolic syndrome. We will specifically examine evidence linking EDC exposures during critical periods of development with metabolic diseases that manifest later in life and across generations

Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of Disease Study 2017

Background Although the burden of influenza is often discussed in the context of historical pandemics and the threat of future pandemics, every year a substantial burden of lower respiratory tract infections (LRTIs) and other respiratory conditions (like chronic obstructive pulmonary disease) are attributable to seasonal influenza. The Global Burden of Disease Study (GBD) 2017 is a systematic scientific effort to quantify the health loss associated with a comprehensive set of diseases and disabilities. In this Article, we focus on LRTIs that can be attributed to influenza. Methods We modelled the LRTI incidence, hospitalisations, and mortality attributable to influenza for every country and selected subnational locations by age and year from 1990 to 2017 as part of GBD 2017. We used a counterfactual approach that first estimated the LRTI incidence, hospitalisations, and mortality and then attributed a fraction of those outcomes to influenza. Findings Influenza LRTI was responsible for an estimated 145 000 (95% uncertainty interval [UI] 99 000–200 000) deaths among all ages in 2017. The influenza LRTI mortality rate was highest among adults older than 70 years (16·4 deaths per 100 000 [95% UI 11·6–21·9]), and the highest rate among all ages was in eastern Europe (5·2 per 100 000 population [95% UI 3·5–7·2]). We estimated that influenza LRTIs accounted for 9 459000 (95% UI 3 709000–22 935000) hospitalisations due to LRTIs and 81 536 000 hospital days (24 330 000–259851 000). We estimated that 11·5% (95% UI 10·0–12·9) of LRTI episodes were attributable to influenza, corresponding to 54481 000 (38465000–73864000) episodes and 8172000 severe episodes (5 000 000–13 296000). Interpretation This comprehensive assessment of the burden of influenza LRTIs shows the substantial annual effect of influenza on global health. Although preparedness planning will be important for potential pandemics, health loss due to seasonal influenza LRTIs should not be overlooked, and vaccine use should be considered. Efforts to improve influenza prevention measures are needed

Lesula: A New Species of Cercopithecus Monkey Endemic to the Democratic Republic of Congo and Implications for Conservation of Congo’s Central Basin

In June 2007, a previously undescribed monkey known locally as “lesula” was found in the forests of the middle Lomami Basin in central Democratic Republic of Congo (DRC). We describe this new species as Cercopithecus lomamiensis sp. nov., and provide data on its distribution, morphology, genetics, ecology and behavior. C. lomamiensis is restricted to the lowland rain forests of central DRC between the middle Lomami and the upper Tshuapa Rivers. Morphological and molecular data confirm that C. lomamiensis is distinct from its nearest congener, C. hamlyni, from which it is separated geographically by both the Congo (Lualaba) and the Lomami Rivers. C. lomamiensis, like C. hamlyni, is semi-terrestrial with a diet containing terrestrial herbaceous vegetation. The discovery of C. lomamiensis highlights the biogeographic significance and importance for conservation of central Congo’s interfluvial TL2 region, defined from the upper Tshuapa River through the Lomami Basin to the Congo (Lualaba) River. The TL2 region has been found to contain a high diversity of anthropoid primates including three forms, in addition to C. lomamiensis, that are endemic to the area. We recommend the common name, lesula, for this new species, as it is the vernacular name used over most of its known range

Geographic patterns of mtDNA and Z-linked sequence variation in the Common Chiffchaff and the ‘chiffchaff complex’

We are grateful to the University of Washington Burke Museum (UWBM), US National Museum of Natural History (USNM), National History Museum Belgrade (NHMBEO), State Darwin Museum (SDM), Zoological Museum of Moscow State University (MSUZM), Yale Peabody Museum (YPM), University of Minnesota Bell Museum (MMNH), Texas A&M University Biodiversity Research and Teaching Collections (TCWC), Staffan Bensch, Stephen Menzie and Nigel Odin for sample loans. This is publication number 1585 of the Biodiversity Research and Teaching Collections at Texas A&M University. Funding: This work was supported by FEDER funds through the COMPETE programme, POPH/QREN/FSE funds to S.V.D. and NORTE2020/PORTUGAL funds (NORTE-01-0145-FEDER-AGRIGEN) to R.J.L., by the Fundação para a Ciência e a Tecnologia/MEC to S.V.D. (FCOMP-01-0124-FEDER-008941; PTDC/BIA- BEC/103435/2008) and R.J.L (SFRH/BPD/84141/2012), by the National Geographic Society to S.V.D, by Torino University Grant ex 60% 2017 and 2018 to M. P. and by Ministarstvo Kulture I Informisanja Republike Srbije (Project: Ptice zapadnog palearktika) to M.R. The Russian Science Foundation grant No. 14-50-00029 'Scientific basis of the national biobank – depository of living systems' (to E.A.K). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Russian Science Foundation grant No. 14-50-00029 'Scientific basis of the national biobank – depository of living systems' (to E.A.K).Peer reviewedPublisher PD