Репозиторий Университета

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Recent strides in micro-and nanofabrication technology have enabled researchers to design and develop new micro-and nanorobots for biomedicine and environmental monitoring. Due to its non-invasive remote actuation and convenient navigation abilities, magnetic propulsion has been widely used in micro-and nanoscale robotic systems. In this article, a highly efficient Janus microdimer swimmer propelled by a rotating uniform magnetic field was investigated experimentally and numerically. The velocity of the Janus microdimer swimmer can be modulated by adjusting the magnetic field frequency with a maximum speed of 133 µm·s−1 (≈13.3 body length s−1) at the frequency of 32 Hz. Fast and accurate navigation of these Janus microdimer swimmers in complex environments and near obstacles was also demonstrated. This efficient propulsion behavior of the new Janus microdimer swimmer holds considerable promise for diverse future practical applications ranging from nanoscale manipulation and assembly to nanomedicine.

© 2019, MDPI AG. All rights reserved. Tuberculosis is known to be the biggest global health problem, causing the most deaths by a single infectious agent. Vaccine-development efforts are extremely important. This paper represents the results of the first-in-human trial of recombinant subunit tuberculosis vaccine GamTBvac in a Phase I study. GamTBvac is a new BCG booster candidate vaccine containing dextran-binding domain modified Ag85a and ESAT6-CFP10 MTB antigens and CpG ODN adjuvant, formulated with dextrans. Safety and immunogenicity of GamTBvac were estimated in an open-label clinical trial on 60 Mycobacterium tuberculosis uninfected (MTB-uninfected) volunteers previously-vaccinated with Bacillus Calmette—Guérin vaccine (BCG). The candidate vaccine had an acceptable safety profile and was well-tolerated. Three different vaccine doses with a double-immunization scheme were assessed for immunogenicity and induced a significant increase in IFN-γ in-house IGRA response and IgG ELISA analysis. Among them, the half dose vaccine group (containing DBD-ESAT6-CFP10, 12.5 μg; DBD-Ag85a, 12.5 μg; CpG (ODN 2216), 75 μg; DEAE-Dextran 500 kDa, 250 μg; and Dextran 500 kDa, 5 mg) provided high, early and stable in time immune response specific to both protein antigen fusions and is proposed for the further studies.

© 2019 Elsevier Inc. Air pollution caused by vehicle emissions remains a serious environmental threat in urban areas. Sedimentation of atmospheric aerosols, surface wash, drainage water, and urbane wastewater can bring vehicle particle emissions into the aquatic environment. However, the level of toxicity and mode of toxic action for this kind of particles are not fully understood. Here we explored the aquatic toxic effects of particulate matter emitted from different types of vehicles on marine microalgae Porphyridium purpureum and Heterosigma akashiwo. We used flow cytometry to evaluate growth rate inhibition, changes in the level of esterase activity, changes in membrane potential and size changes of microalgae cells under the influence of particulate matter emitted by motorcycles, cars and specialized vehicles with different types of engines and powered by different types of fuel. Both microalgae species were highly influenced by the particles emitted by diesel-powered vehicles. These particle samples had the highest impact on survival, esterase activity, and membrane potential of microalgae and caused the most significant increase in microalgae cell size compared to the particles produced by gasoline-powered vehicles. The results of the algae-bioassay strongly correlate with the data of laser granulometry analyses, which indicate that the most toxic samples had a significantly higher percentage of particles in the size range less than 1 μm. Visual observation with an optical microscope showed intensive agglomeration of the particles emitted by diesel-powered vehicles with microalgae cells. Moreover, within the scope of this research, we did not observe the direct influence of metal content in the particles to the level of their aquatic toxicity, and we can conclude that physical damage is the most probable mechanism of toxicity for vehicle emitted particles.

© 2019 Elsevier B.V. Cannabis policies are changing globally, and medical marijuana programs are part of these changes. Drawing from the examples of two high-income (Canada, an early adopter of medical marijuana, and Germany, a late adopter) and one middle-income (Thailand) countries, we illustrate two main pressures underlying these recent changes. First, in many high-income countries, cannabis has been used to self-medicate for different ailments and diseases, even though there is no evidence of effectiveness for many of these conditions. Second, the cannabis industry is pressuring governments and decision-makers to allow for medical marijuana use with lenient regulations—without specifying medical conditions (indications) and requiring only a prescription from a health professional to obtain it. As a result, demand is likely to increase, even in countries with low prevalence of use. Cannabis policy-makers need to consider a balance between the medical benefits of medical marijuana and the potential public health consequences and cost.

© 2018 Elsevier Ltd An excessive inflammatory response is frequently associated with cellular dysfunction and cell death. The latter may cause single and multiple organ failure. The most susceptible organs are liver, lung, kidney, heart and intestine. This review will focus on the liver as a target organ for an excessive inflammatory response. It is commonly accepted that organ failure is caused by the action of inflammatory cytokines released in excess during the inflammatory response. It has been suggested that inflammation mediated liver failure is not due to an increased death rate of parenchymal cells, but due to an intracellular metabolic disorder. This metabolic disorder is associated with mitochondrial and endoplasmic reticulum (ER) dysfunction during the acute phase response elicited by systemic inflammation. An overproduction of acute phase proteins in the liver as well as elevated reactive oxygen species (ROS) generation induce ER stress, triggering the unfolded protein response (UPR), which may initiate or aggravate inflammation. It is known that certain inflammatory mediators, such as the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α induce ER stress. These findings suggest that ER stress and the subsequent UPR on the one hand, and the inflammatory response on the other create a kind of feed forward loop, which can be either beneficial (e.g., elimination of the pathogen and restoration of tissue homeostasis) or deleterious (e.g., excessive cell dysfunction and cell death). This review aims to unfurl the different pathways contributing to this loop and to highlight the relevance of UPR signaling (IRE1α, ATF6, and PERK) and mediators of the inflammatory response (NF-κB, STAT3, IL-1β, IL-6, TLR) which have a particular role as pathophysiological triggers in the liver.

© 2019 Elsevier GmbH Background: Data on the association between aluminium (Al) exposure and obesity and/or metabolic syndrome are insufficient. The objective of the present study was to investigate the association between hair and urine Al levels and obesity. Methods: A total of 206 lean and 205 obese non-occupationally exposed subjects (30–50 y.o.) were enrolled in the study. Hair and urine Al levels were assessed with ICP-MS. Laboratory quality control was performed using the certified reference materials of human hair, plasma, and urine. Results: Hair and urinary Al levels in obese subjects were significantly higher by 31% and 46% compared to the control levels, respectively. The presence of hypertension (41% cases), atherosclerosis (8%), type 2 diabetes mellitus (10%), and non-alcoholic fatty liver disease (NAFLD) (53%) in obese patients were not associated with Al levels in the studied subjects. An overall multiple regression model established urinary Al levels (β = 0.395; p < 0.001), hypertension (β = 0.331; p < 0.001) and NAFLD (β = 0.257; p = 0.003) were significantly and directly associated with BMI. Hair Al levels were found to be border-line significantly related to BMI after adjustment for several confounders (β = −0.205; p = 0.054). Conclusions: Aluminium body burden is associated with increased body weight, although the causal relationship between Al exposure and obesity is not clear. Both clinical and experimental studies are required to further investigate the impact of Al exposure on metabolic parameters in obesity and especially direct effects of Al in adipose tissue.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Protein phosphorylation/dephosphorylation is an important regulatory mechanism that controls many key physiological processes. Numerous pathogens successfully use kinases and phosphatases to internalize, replicate, and survive, modifying the host’s phosphorylation profile or signal transduction pathways. Multiple phosphatases and kinases from diverse bacterial pathogens have been implicated in human infections before. In this work, we have identified and characterized the dual specificity protein/lipid phosphatase LmDUSP1 as a novel virulence factor governing Leishmania mexicana infection. The LmDUSP1-encoding gene (LmxM.22.0250 in L. mexicana) has been acquired from bacteria via horizontal gene transfer. Importantly, its orthologues have been associated with virulence in several bacterial species, such as Mycobacterium tuberculosis and Listeria monocytogenes. Leishmania mexicana with ablated LmxM.22.0250 demonstrated severely attenuated virulence in the experimental infection of primary mouse macrophages, suggesting that this gene facilitates Leishmania pathogenicity in vertebrates. Despite significant upregulation of LmxM.22.0250 expression in metacyclic promastigotes, its ablation did not affect the ability of mutant cells to differentiate into virulent stages in insects. It remains to be further investigated which specific biochemical pathways involve LmDUSP1 and how this facilitates the parasite’s survival in the host. One of the interesting possibilities is that LmDUSP1 may target host’s substrate(s), thereby affecting its signal transduction pathways.

© 2019 Elsevier Inc. Welding fumes are a major source of metal oxide particles, ozone, carbon monoxide, carbon dioxide, nitrogen oxides, and many other toxic substances. Hazardous properties and the level of toxicity of welding fumes depend mostly on the welding electrode type and the welding regime parameters. The specific objective of this study was to evaluate the aquatic toxicity of metal welding fume particles in vivo on microalga Heterosigma akashiwo. The quantity and size of particles were measured by flow cytometry using a scattering laser light with a wavelength of 405 nm. The number of microalgae cells after 72 h and 7 days exposition with welding fume particle suspensions was evaluated by flow cytometry. Morphological changes of the microalga were observed by optical microscopy. The toxic effect was demonstrated as a significant reduction of cell density after exposure of microalgae to welding fume particles. The greatest impact on the growth of microalga was caused by particles with high rutile content. It was shown that the adverse effect of metal oxide particles depends more on the chemical composition of particles in welding fume while the number and dispersity of particles had no noticeable toxic influence on microalgae. The findings of this research confirm the fact that the toxicity of welding fume particles can be significantly reduced by using rutile-cellulose coated electrodes.

© 2019 Rad51 is a key protein in DNA repair by homologous recombination and an important target for development of drugs in cancer therapy. 4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) has been used in clinic during the past 30 years as an inhibitor of anion transporters and channels. Recently DIDS has been demonstrated to affect Rad51-mediated homologous pairing and strand exchange, key processes in homologous recombination. Consequently, DIDS has been considered as a potential revertant of radio- and chemo-resistance of cancer cells, the major causes of therapy failure. Here, we have investigated the behavior of DIDS towards serum albumins. The effects of environmental factors, primarily, solvent polarity, on DIDS stability were evaluated, and the mechanisms of interaction of DIDS with human or bovine serum albumin were analyzed using isothermal calorimetry, circular dichroism and fluorescence spectroscopies. DIDS interaction with both serum albumins have been demonstrated, and the interaction characteristics have been determined. By comparing these characteristics for several DIDS derivatives, we have identified the DIDS moiety essential for the interaction. Furthermore, site competition data indicate that human albumin has two DIDS-binding sites: a high-affinity site in the IIIA subdomain and a low-affinity one in the IB subdomain. Molecular docking has revealed the key molecular moieties of DIDS responsible for its interactions in each site and shown that the IB site can bind two ligands. These findings show that binding of DIDS to serum albumin may change the balance between the free and bound DIDS forms, thereby affecting its bioavailability and efficacy against Rad51.

© 2019 Elsevier Inc. Hyponatremia has been associated with an increased risk of demise in several malignancies. The aim of the current study was to evaluate its prognostic value in patients with castration-resistant prostate cancer. In 186 patients planned for docetaxel chemotherapy, we detected an association between hyponatremia and decreased survival (P = .04). We suggest conducting further well-designed studies including full workup of hyponatremia.

© 2019 Elsevier GmbH Introduction: Eastern and North-Eastern regions of Kazakhstan are considered to be environmentally disadvantaged due to industrial pollution and activity of the former Semipalatinsk Nuclear Test Site. Ferrous metallurgy is represented by the world's largest ferroalloy plant located in Aksu. In addition to a ferroalloy plant, Aksu is the home for the largest thermal power plant in Kazakhstan. Objective: Biomonitoring of 31 hair and blood trace elements (Ag, Ba, Be, Bi, Cs, Co, Ce, Cr, Cu, Eu, Gd, Hf, In, La, Li, Mn, Mo, Nb, Nd, Pb, Sc, Sn, Tl, Th, U, V, W, Y, Yb, Zn, and Zr) in non-occupationally exposed population residing in polluted areas of East Kazakhstan and Pavlodar regions. Methods: Five case groups, residing in the vicinity to the former Semipalatinsk Nuclear Test Site (Akzhar, Borodulikha, and Karaul) or in proximity to industrial plants (Aksu and Ust-Kamenogorsk) have been assessed vs. controls from a rural settlement in Kurchum. In total, 204 hair and blood samples were analyzed by inductively coupled plasma mass spectrometry. Results: The observed blood concentrations of trace elements were in agreement with earlier studies on residents of industrially polluted areas. Elevated levels of blood Ba, Mn, Pb, V, and Zn were detected in residents of Aksu and Ust-Kamenogorsk. The elemental composition of head hair was characterized by greater stability between the study sites. Conclusion: Residency near the former Semipalatinsk Test Site could be considered as safe, while the environmental status of industrial settlements appears to be rather adverse.

© 2019 Australian Society for Parasitology The extreme biological diversity of Oceanian archipelagos has long stimulated research in ecology and evolution. However, parasitic protists in this geographic area remained neglected and no molecular analyses have been carried out to understand the evolutionary patterns and relationships with their hosts. Papua New Guinea (PNG) is a biodiversity hotspot containing over 5% of the world's biodiversity in less than 0.5% of the total land area. In the current work, we examined insect heteropteran hosts collected in PNG for the presence of trypanosomatid parasites. The diversity of insect flagellates was analysed, to our knowledge for the first time, east of Wallace's Line, one of the most distinct biogeographic boundaries of the world. Out of 907 investigated specimens from 138 species and 23 families of the true bugs collected in eight localities, 135 (15%) were infected by at least one trypanosomatid species. High species diversity of captured hosts correlated with high diversity of detected trypanosomatids. Of 46 trypanosomatid Typing Units documented in PNG, only eight were known from other geographic locations, while 38 TUs (~83%) have not been previously encountered. The widespread trypanosomatid TUs were found in both widely distributed and endemic/sub-endemic insects. Approximately one-third of the endemic trypanosomatid TUs were found in widely distributed hosts, while the remaining species were confined to endemic and sub-endemic insects. The TUs from PNG form clades with conspicuous host-parasite coevolutionary patterns, as well as those with a remarkable lack of this trait. In addition, our analysis revealed new members of the subfamilies Leishmaniinae and Strigomonadinae, potentially representing new genera of trypanosomatids.

© 2019 The purpose of this study was to assess the prognostic value of lactate dehydrogenase (LDH) in patients with metastatic prostate cancer (PC). A systematic review and meta-analysis was performed in March 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with PC with high versus low LDH to determine the predictive value of LDH for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We performed a formal meta-analysis for both OS and PFS. A total of 59 articles with 14,851 patients were included in the systematic review and 45 studies with 12,224 patients for the qualitative assessment. High LDH was associated with both worse OS (pooled hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.75-2.44) and PFS (pooled HR, 1.08; 95% CI, 1.01-1.16). In subgroup analyses of both patients with castration-resistant prostate cancer (CRPC) and those with hormone-sensitive prostate cancer (HSPC), LDH was associated with OS (pooled HR, 2.02; 95% CI, 1.69-2.42 and pooled HR, 2.25; 95% CI, 1.78-2.84, respectively). In patients with CRPC, LDH was associated with OS in those treated with docetaxel systemic chemotherapy and androgen receptor–axis-targeting agents (pooled HR, 2.03; 95% CI, 1.37-3.00 and pooled HR, 1.79; 95% CI, 1.25-2.57, respectively). Elevated serum levels of LDH were associated with an increased risk of mortality and progression in patients with metastatic PC. LDH was independently associated with OS in both patients with CRPC and HSPC. LDH could be integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision-making process.

© 2019 Wiley Periodicals, Inc. Background: To test the effect of radical cystectomy (RC) with chemotherapy vs only chemotherapy on overall mortality (OM) in metastatic urothelial carcinoma of the urinary bladder (mUCUB). Methods: Within the Surveillance, Epidemiology, and End Results registry (2004–2016), we identified patients with mUCUB. Stratification was made according to treatment: RC with chemotherapy vs only chemotherapy. Kaplan-Meier plots and multivariable Cox regression models were used before and after 1:1 propensity score (PS) matching and inverse probability of treatment weighting (IPTW). Results: Of 2414 patients with mUCUB, 500 (21.0%) vs 1914 (79.0%) were treated with RC with chemotherapy vs only chemotherapy, respectively. In multivariable Cox regression models, RC with chemotherapy was associated with lower OM in the overall cohort (hazard ratio [HR], 0.5; P <.001), after 1:1 PS matching (HR, 0.5; P <.001), after IPTW (HR, 0.5; P <.001) and after accounting for number and location of metastases (HR, 0.5; P <.001). However, higher overall survival after RC with chemotherapy was only observed in patients with one metastatic site (21 vs 16 months; P =.001). Conclusion: In contemporary patients with mUCUB, RC with chemotherapy is associated with lower OM rates, relative to chemotherapy alone, but only in patients with a single metastatic site. These individuals accounted for the vast majority of patients in whom an RC was performed, despite the presence of metastatic disease.

© 2019 The Author(s). Background: Over the last decade Russia has introduced various policy measures to reduce alcohol consumption and alcohol-related harm at the population level. Several of these policies, such as higher pricing and taxation or restrictions of availability, may not work in the case of unrecorded alcohol consumption; they may encourage consumers to switch to unrecorded alcohol and even increase consumption. In the present qualitative interview study we explore the perception of the recently implemented alcohol policies by patients diagnosed with alcohol dependence in two Russian cities in the years 2013-2014 and shed light on possible entry-points to prevention. Methods: Semi-structured in-depth expert interviews were conducted with 25 patients of state-run drug and alcohol treatment centers in two Russian cities in 2013 and 2014. The interviews were analyzed using thematic content analysis. Results: All of the interviewed participants have consumed unrecorded at some point with the majority being regular consumers, mostly switching between recorded and unrecorded alcohol depending on the situation, as predominantly defined by available money and available sources of alcohol. Low price and high availability were reported as the main reasons for unrecorded consumption. Participants voiced a general mistrust of the recently implemented alcohol regulations and viewed them largely as ineffective. They expressed particular concerns over price increases and restriction of night sales of alcoholic beverages. Substantial shifts within the unrecorded alcohol market were reported, with a decreasing availability of home-made beverages in favor of alcohol surrogates in the form of non-beverage alcohol, medicinal and cosmetic compounds. At the same time consumption of home-made alcoholic beverages was seen as a strategy to avoid counterfeit alcohol, which was frequently reported for retail sale. Conclusions: Despite the alcohol policy changes in the last years in Russia, consumption of unrecorded alcohol remained common for people with alcohol dependence. Reduction of availability of unrecorded alcohol, first and foremost in the form of cheap surrogates, is urgently needed to reduce alcohol-related harm. Implementation of screening and brief interventions for excessive alcohol consumption in various contexts such as primary healthcare settings, trauma treatment services or the workplace could be another important measure targeting consumers of unrecorded alcohol.

BACKGROUND: This retrospective clinical study aims to present results of experience with a novel guided surgery system with a sleeveless, open-frame structure, in which the surgical handpiece (not the drills used for preparation) is guided. METHODS: This study was based on an evaluation of the records of partially edentulous patients who had been treated with a sleeveless open-frame guided surgery system (TWIN-Guide®, 2Ingis, Brussels, Belgium), between January 2015 and December 2017. Inclusion criteria were patients with good systemic/oral health and a minimum follow-up of 1 year. Exclusion criteria were patients who had been treated without a guide, or with a guide with sleeves, patients with systemic/oral diseases and who did not have a follow-up of 1 year. The main outcomes were surgical (fit and stability of the surgical guide, duration of the intervention, implant stability, and any intra-operative or immediate post-operative complication), biologic, and prosthetic. RESULTS: Thirty-eight patients (24 males, 14 females; mean age 56.5 ± 14.0 years) were included in the study. These patients had been treated with 110 implants inserted by means of 40 sleeveless, open-frame guides. With regard to fit and stability, 34 guides were excellent, 4 acceptable, and 2 inadequate for use. The mean duration of the intervention was 23.7 (± 6.7) minutes. Immediately after placement, 2 fixtures were not stable and had to be removed. Two patients experienced pain/swelling after surgery. The 108 surviving implants were restored with 36 single crowns and 32 fixed partial prostheses (24 two-unit and 8 three-unit bridges); these restorations survived until the 1-year follow-up, with a low incidence of biologic and prosthetic complications. CONCLUSIONS: Within the limits of this study, this novel guided surgery system with sleeveless, open frame-structure guides seems to be clinically reliable; further studies on a larger sample of patients are needed to confirm these outcomes.

© 2019 The Author(s). Background: The aim of this study was to compare free fluoride concentration and total fluoride concentration in mouthwashes. Methods: Fluorine-containing mouthwashes from various companies and manufacturers (Colgate Total Plax Classic Mint®, Colgate-Palmolive, New York, USA; Colgate Total Plax Gentle Mint®, Colgate-Palmolive, New York, USA; Colgate Total Plax Fresh Mint®, Colgate-Palmolive, New York, USA; Oral B Advantage®, Procter&Gamble, Cincinnati, USA; Reach Fresh Mint®, Johnson&Johnson, New Brunswick, USA; Foramen®, Laboratorios Foramen, Guarnizo, Spain; Lacalut Sensitive®, Dr. THEISS, Homburg, Germany; Sensodyne®, GlaxoSmithKline, London, UK; Vesna F®, Vita, Saint Petersburg, Russia; Lacalut Fresh®, Dr. THEISS, Homburg, Germany) were selected as study objects. Fluoride measurements were carried out using the fluoride selective electrode. Results: Free fluoride:total fluoride ratio was more than 80% for six samples (Colgate Total Plax Gentle Mint® - 88%, Colgate Total Plax Fresh Mint® - 99%, Oral B Advantage® - 92%, Reach Fresh Mint® - 92 and 89% for the mouthwash of another batch, Lacalut Sensitive® - 94%) and less than 63% for three samples (Colgate Total Plax Classic Mint® - 56%, Foramen® - 62%, Vesna F® - 61%). Two samples had more than 70% and less than 80% of unbound fluoride, respectively (Sensodyne® - 77%, another batch of Oral B Advantage® mouthwash - 74%). Rinse containing sodium monofluorophosphate (Na2PO3F) (Vesna F®) had more than 50% of free fluoride, while the rinse containing amine fluoride (AmF) (Lacalut Sensitive®) had 94%. The difference in the free fluoride:total fluoride ratio can be explained by binding of fluoride ions by components contained in mouthwashes, such as coloring agents and polymeric compounds. The lowest concentration of free fluoride ions (0.000093 mol/L) was observed for aluminum fluoride (AlF3) rinse (Lacalut Fresh®), while the total fluoride amount was not determined due to possible generation of strong fluoride complexes. This implies that fluoride ions will not be uptaken by tooth tissue and may even be washed away from it, compromising the efficacy of mouthwashes. Conclusions: The differences in free fluoride: total fluoride ratio between analyzed mouthwashes reveal a need to develop a method for evaluation of free fluorides in mouthwashes for proper updating of national and international guidelines.

© 2019 Elsevier B.V. Most of the on-site approaches for inferring of the post-mortem interval are still based on observative data from the direct body inspection, whereas, objective and quantitative analyses, such as potassium in the vitreous humor, are require laboratory instrumentation and skilled personnel. The present paper presents a simple and low cost analytical method suitable for use at the crime scene for inferring the time since death. The method uses a microfluidic paper-based device (μPAD) for the determination of ammonium in the vitreous humor (VH) based on the selective interaction between the ammonium and the Nessler's reagent. The color change was measured in terms of “RGB distance” by using a simple and free smartphone application. The optimized device showed a limit of detection of 0.4 mmol L−1, with between days precision less than 9.3% expressed as relative standard deviation, and accuracy between days from 94.5% to 104.5%. The selectivity of the Nessler's reaction was tested towards the main vitreous humor compounds, and no significant interferences were found. This paper-based analytical device was successfully used for the determination of ammonium ion in VH samples from forensic autopsies. The results obtained with the proposed method, although for a limited number of cases (n = 25), showed a close correlation with the data obtained with an instrumental analysis based on capillary electrophoresis. Moreover, in order to make the evaluation of results as simple as possible, a direct correlation between the color intensity, expressed as RGB distance, and the post-mortem interval was studied and a significant correlation was found (R2 > 0.78). In conclusion, the present preliminary study showes that the proposed device could be an additional tool to the traditional methods for a more accurate, although still presumptive, estimation of the time of death directly at the crime scene.

© 2019 Elsevier Inc. Loss of dopaminergic neurons in the substantia nigra is one of the pathogenic hallmarks of Parkinson's disease, yet the underlying molecular mechanisms remain enigmatic. While aberrant redox metabolism strongly associated with iron dysregulation and accumulation of dysfunctional mitochondria is considered as one of the major contributors to neurodegeneration and death of dopaminergic cells, the specific anomalies in the molecular machinery and pathways leading to the PD development and progression have not been identified. The high efficiency and relative simplicity of a new genome editing tool, CRISPR/Cas9, make its applications attractive for deciphering molecular changes driving PD-related impairments of redox metabolism and lipid peroxidation in relation to mishandling of iron, aggregation and oligomerization of alpha-synuclein and mitochondrial injury as well as in mechanisms of mitophagy and programs of regulated cell death (apoptosis and ferroptosis). These insights into the mechanisms of PD pathology may be used for the identification of new targets for therapeutic interventions and innovative approaches to genome editing, including CRISPR/Cas9.

© 2019 The Author(s). Background: Resting-state functional connectivity (FC) MRI has widely been used to understand migraine pathophysiology and to identify an imaging marker of the disorder. Here, we review what we have learned from FC studies. Methods: We performed a literature search on the PubMed website for original articles reporting data obtained from conventional resting-state FC recording in migraine patients compared with healthy controls or during and outside of migraine attacks in the same patients. Results: We found 219 articles and included 28 in this review after screening for inclusion and exclusion criteria. Twenty-five studies compared migraine patients with healthy controls, whereas three studies investigated migraine patients during and outside of attacks. In the studies of interictal migraine more alterations of more than 20 FC networks (including amygdala, caudate nucleus, central executive, cerebellum, cuneus, dorsal attention network, default mode, executive control, fronto-parietal, hypothalamus, insula, neostriatum, nucleus accumbens, occipital lobe, periaqueductal grey, prefrontal cortex, salience, somatosensory cortex I, thalamus and visual) were reported. We found a poor level of reproducibility and no migraine specific pattern across these studies. Conclusion: Based on the findings in the present review, it seems very difficult to extract knowledge of migraine pathophysiology or to identify a biomarker of migraine. There is an unmet need of guidelines for resting-state FC studies in migraine, which promote the use of homogenous terminology, public availability of protocol and the a priori hypothesis in line with for instance randomized clinical trial guidelines.