Infectivity of Leishmania donovani amastigotes and promastigotes for golden hamsters.
Intracardial injection of hamsters with from 5 to 114 million amastigotes or promastigotes of Leishmania donovani and screening of the 8th-day liver impression smears, provides a rapid and reproducible method for assaying infectivity. Amastigotes are at least 10X more infective than promastigotes, and log-phase promastigotes act as a single infective population for hamsters.


Enhanced photocatalytic H2 production on CdS nanorods with simple molecular bidentate cobalt complexes as cocatalysts under visible light.
Photocatalytic hydrogen production via water splitting has attracted much attention for future clean energy application. Herein we report a noble-metal-free photocatalytic hydrogen production system containing a simple bidentate cobalt Schiff base complex as the molecular cocatalyst, CdS nanorods as the photosensitizer, and ascorbic acid as the electron donor. The system shows highly enhanced photocatalytic activity compared to pure CdS NRs under visible light (λ > 420 nm). Under optimal conditions, the turnover numbers (TONs) for hydrogen production reached ∼15 200 after 12 hours of irradiation, and an apparent quantum yield of ∼27% was achieved at 420 nm monochromatic light. Steady-state photoluminescence (PL) spectra indicated efficient charge transfer between the excited CdS NRs and the cobalt cocatalyst for improved hydrogen production. Spectroscopic studies of the photocatalytic reaction revealed the reduction of the Co(ii) complex to Co(i) species, which are probably active intermediates for hydrogen evolution. On the basis of the spectroscopic studies, we propose a reaction mechanism for hydrogen production in the present photocatalytic system.


Tetrameric psuedo-peptide receptors with allosteric properties.
This paper reports the binding properties of tetrameric pseudo-peptide receptors for protonated cytidines. The receptors, which were isolated from a dynamic combinatorial chemistry (DCC) experiment, bind the analytes with affinities that depend on the presence or absence of excess acid, and with a stoichiometry that is both concentration and temperature dependent.


Successful treatment of gangrene in systemic necrotizing vasculitis with iloprost.
Systemic necrotizing vasculitis is uncommon in children and may be rarely associated with gangrene. We describe a 3-yr-old girl with parvovirus B19-induced necrotizing vasculitis whose digital gangrene was successfully treated with iloprost, a prostacyclin analogue.


* Comparison of Autologous, Allogeneic, and Cell-Free Scaffold Approaches for Engineered Tendon Repair in a Rabbit Model-A Pilot Study.
Tendons are subjected to high strength dynamic mechanical forces in vivo. Mechanical strength is an essential requirement for tendon scaffold materials. A composite scaffold was used in this study to provide mechanical strength, which was composed of an inter part of nonwoven polyglycolic acid (PGA) fibers and an outer part of the net knitted with PGA and polylactic acid (PLA) fibers in a ratio of 4:2. This study compared three different approaches for in vivo tendon engineering, that is, cell-free scaffold and allogeneic and autologous cell seeded scaffolds, using a rabbit Achilles tendon repair model. Dermal fibroblasts were, respectively, isolated from the dermis of regular rabbits or green fluorescence protein transgenic rabbits as the autologous and the allogeneic cell sources, respectively. The cell scaffolds and cell-free scaffolds were implanted to bridge a partial segmental defect of rabbit Achilles tendon. The engineered tendons were harvested at 7 and 13 months postsurgery for various examinations. The results showed that all three groups could achieve in vivo tendon regeneration similarly with slightly better tissue formation in autologous group than in other two groups, including better scaffold degradation and relatively thicker collagen fibrils. There were no statistically significant differences in mechanical parameters among three groups. This work demonstrated that allogeneic fibroblasts and scaffold alone are likely to be used for tendon tissue engineering.


Olfactory sensitivity for aliphatic alcohols in squirrel monkeys and pigtail macaques.
The view that primates are microsmatic animals is based mainly on an interpretation of neuroanatomical features, whereas physiological evidence of a poorly developed sense of smell in this order of mammals is largely lacking. Using a conditioning paradigm, we therefore assessed the olfactory sensitivity of three squirrel monkeys (Saimiri sciureus) and of four pigtail macaques (Macaca nemestrina) for a homologous series of aliphatic alcohols (ethanol to 1-octanol) and isomeric forms of some of these substances. In the majority of cases, the animals of both species significantly discriminated concentrations below 1 part per million from the odourless solvent, and with 1-hexanol individual monkeys even demonstrated thresholds below 10 parts per billion. The results showed (i) that both primate species have a well-developed olfactory sensitivity for aliphatic alcohols, which for the majority of substances matches or even is better than that of species such as the rat, (ii) that both species generally show very similar olfactory detection thresholds for aliphatic alcohols, and (iii) that a significant negative correlation between perceptibility in terms of olfactory detection threshold and carbon chain length of both the aliphatic 1- and 2-alcohols exists in both species. These findings support the idea that across-species comparisons of neuroanatomical features are a poor predictor of olfactory performance and that general labels such as 'microsmat' or 'macrosmat', which are usually based on allometric comparisons of olfactory brain structures, are inadequate to describe the olfactory capabilities of a species. Further, our findings suggest that olfaction may play an important and hitherto underestimated role in the regulation of behaviour in the species tested.


High-resolution mapping of the global silicate weathering carbon sink and its long-term changes.
Climatic and non-climatic factors affect the chemical weathering of silicate rocks, which in turn affects the CO2 concentration in the atmosphere on a long-term scale. However, the coupling effects of these factors prevent us from clearly understanding of the global weathering carbon sink of silicate rocks. Here, using the improved first-order model with correlated factors and non-parametric methods, we produced spatiotemporal data sets (0.25° × 0.25°) of the global silicate weathering carbon-sink flux (SCSFα ) under different scenarios (SSPs) in present (1950-2014) and future (2015-2100) periods based on the Global River Chemistry Database and CMIP6 data sets. Then, we analyzed and identified the key regions in space where climatic and non-climatic factors affect the SCSFα . We found that the total SCSFα was 155.80 ± 90 Tg C yr-1 in present period, which was expected to increase by 18.90 ± 11 Tg C yr-1 (12.13%) by the end of this century. Although the SCSFα in more than half of the world was showing an upward trend, about 43% of the regions were still showing a clear downward trend, especially under the SSP2-4.5 scenario. Among the main factors related to this, the relative contribution rate of runoff to the global SCSFα was close to 1/3 (32.11%), and the main control regions of runoff and precipitation factors in space accounted for about 49% of the area. There was a significant negative partial correlation between leaf area index and silicate weathering carbon sink flux due to the difference between the vegetation types. We have emphasized quantitative analysis the sensitivity of SCSFα to critical factors on a spatial grid scale, which is valuable for understanding the role of silicate chemical weathering in the global carbon cycle.


Conditioned media from human ovarian cancer endothelial progenitor cells induces ovarian cancer cell migration by activating epithelial-to-mesenchymal transition.
Bone marrow-derived endothelial progenitor cells (EPCs) migrate to and engraft at ovarian cancer sites. Understanding the interactions between ovarian cancer cells and EPCs is fundamental for determining whether to harness EPC-tumor interactions for delivery of therapeutic agents or target them for intervention. Ovarian cancer cell lines (SKOV-3 and OVCAR-3) were cultured alone or in EPC-conditioned media (EPC-CM). Migration of ovarian cancer cells was detected by transwell chamber. N-cadherin and E-cadherin expression were analyzed by real-time reverse transcription PCR and western blot. EPC-CM can increase transforming growth factor-beta (TGF-β) secretion in SKOV-3 and OVCAR-3 cells. EPC-CM induced loss of ovarian cancer cell-cell junctions, downregulation of E-cadherin, upregulation of N-cadherin and acquisition of a fibroblastic phenotype, consistent with an epithelial-to-mesenchymal transition (EMT). The specific TGF-β inhibitor SB431542 abolished the SKOV-3 and OVCAR-3 ovarian cancer cell migration induced by EPC-CM. In SKOV-3 and OVCAR-3 cells, EPC-CM downregulated E-cadherin and concurrently upregulated N-cadherin. EPC-CM upregulated the expression of transcriptional repressors of E-cadherin, Snail and Twist. Treatment with SB431542 abolished the effects of EPC-CM on the relative expression levels of cadherin, Snail and Twist. This study demonstrates that TGF-β has a role in EPC-CM-induced ovarian cancer migration by activating EMT.


The PA profession in Israel: A half-decade perspective.
Implementation of physician assistants (PAs) in EDs throughout Israel began in May 2016. The profession is now showing some progress but at a relatively slow rate. This article provides an overview of Israel and its healthcare system, and describes the implementation, deployment, education, training, and scope of practice of PAs in Israel, plus recent developments and suggestions for advancing the profession.


A novel knowledge-based approach to design inorganic-binding peptides.
The discovery of solid-binding peptide sequences is accelerating along with their practical applications in biotechnology and materials sciences. A better understanding of the relationships between the peptide sequences and their binding affinities or specificities will enable further design of novel peptides with selected properties of interest both in engineering and medicine. A bioinformatics approach was developed to classify peptides selected by in vivo techniques according to their inorganic solid-binding properties. Our approach performs all-against-all comparisons of experimentally selected peptides with short amino acid sequences that were categorized for their binding affinity and scores the alignments using sequence similarity scoring matrices. We generated novel scoring matrices that optimize the similarities within the strong-binding peptide sequences and the differences between the strong- and weak-binding peptide sequences. Using the scoring matrices thus generated, a given peptide is classified based on the sequence similarity to a set of experimentally selected peptides. We demonstrate the new approach by classifying experimentally characterized quartz-binding peptides and computationally designing new sequences with specific affinities. Experimental verifications of binding of these computationally designed peptides confirm our predictions with high accuracy. We further show that our approach is a general one and can be used to design new sequences that bind to a given inorganic solid with predictable and enhanced affinity.


An update on respiratory syncytial virus epidemiology: a developed country perspective.
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and young children worldwide, and an important cause of morbidity, hospitalization, and mortality. The infections caused by RSV are seasonal, peaking predictably in the winter months in temperate climates, and in the hottest months and the rainy season in tropical climates. The involvement of the lower respiratory tract, manifest clinically as bronchiolitis or pneumonia, is the hallmark of severe RSV disease. Other indicators of severe disease include requirement for, and duration of, hospitalization, supplemental oxygen, management in an intensive care setting, and mechanical ventilation. Host-related risk factors for severe RSV disease include preterm birth, infection before 6 months of age, chronic lung disease, and congenital heart disease. Environmental risk factors for severe RSV infection include poverty, crowding, exposure to tobacco smoke, and malnutrition. Factors that increase frequency of the infection include young age, multiple gestation, family history of atopy, lack of parental education, household crowding, older school-age siblings, lack of breast feeding, day-care attendance, passive smoke exposure, and discharge from a neonatal intensive care unit between September and December. Recent studies in Europe, North America and Japan have evaluated the number of children affected as well as the medical resources necessary to care for these children. Continuing surveillance is the key to tracking the seasonality, risk factors, morbidity and mortality associated with RSV infection. Epidemiological studies are also the basis for development of appropriate local prevention strategies.


Metabolism of vesnarinone by activated neutrophils: implications for vesnarinone-induced agranulocytosis.
Vesnarinone is an important new drug that significantly decreases mortality rates in severe congestive heart failure; however, its use is associated with a relatively high incidence (approximately 1%) of agranulocytosis. The authors studied its metabolism by activated neutrophils, the target for this toxicity, and evidence pointed to a pathway that involved a reactive iminium ion. Hydrolysis of the iminium ion led to a reactive quinone imine. The same pathway was observed with a combination of myeloperoxidase/hydrogen peroxide/chloride, the major oxidizing system of neutrophils, or hypochlorous acid, which is generated by this system. Activation of the neutrophils could be achieved by phorbol ester or by influenza vaccine and there is evidence to suggest that the administration of influenza vaccine during vesnarinone therapy may increase the risk of agranulocytosis. Incubation of radiolabeled vesnarinone with activated neutrophils led to covalent binding of almost 5% of the drug to the cells. Both the iminium ion and quinone imine generated by hypochlorous acid could be trapped with glutathione. It was proposed that these reactive metabolites, generated by neutrophils or neutrophil precursors in the bone marrow, may be responsible for the vesnarinone-induced agranulocytosis. Factors such as infection or vaccination that activate neutrophils may increase the risk of agranulocytosis.


Finding the best density functional approximation to describe interaction energies and structures of ionic liquids in molecular dynamics studies.
Ionic liquids raise interesting but complicated questions for theoretical investigations due to the fact that a number of different inter-molecular interactions, e.g., hydrogen bonding, long-range Coulomb interactions, and dispersion interactions, need to be described properly. Here, we present a detailed study on the ionic liquids ethylammonium nitrate and 1-ethyl-3-methylimidazolium acetate, in which we compare different dispersion corrected density functional approximations to accurate local coupled cluster data in static calculations on ionic liquid clusters. The efficient new composite method B97-3c is tested and has been implemented in CP2K for future studies. Furthermore, tight-binding based approaches which may be used in large scale simulations are assessed. Subsequently, ab initio as well as classical molecular dynamics simulations are conducted and structural analyses are presented in order to shed light on the different short- and long-range structural patterns depending on the method and the system size considered in the simulation. Our results indicate the presence of strong hydrogen bonds in ionic liquids as well as the aggregation of alkyl side chains due to dispersion interactions.


High and low brushing force in relation to efficacy and gingival abrasion.
Does a high brushing force induce more gingival abrasion than a low (regular) brushing force? Furthermore, what is the effect of a low or high force on the efficacy? Thirty-five non-dental students were selected. All received an appointment prior to which they abstained from oral hygiene for at least 48 h. At baseline the teeth and surrounding tissues were disclosed using Mira-2-Tone disclosing solution. Next, the examiner (PAV) evaluated the number of sites with gingival abrasion and the amount of dental plaque (Quigley & Hein) at 6 surfaces of each tooth. In the absence of this examiner, the subject's teeth were brushed by a hygienist (MP) using the Braun/Oral-B-D17 oscillating rotating toothbrush. Brushing was performed in two randomly selected contra-lateral quadrants for 60 s with either a low force (+/-1.5 N) or high force (+/-3.5 N) and in the opposing quadrants for 60 s with the alternative force. Visual feedback was given to control force. The brush was moved from the distal tooth to the central incisor perpendicular to the tooth surface with an angle of approximately 10-15 degrees towards the gingival margin. Next, the number of sites with abrasion and the remaining plaque were assessed again. The overall baseline gingival abrasion scores were 3.1 and 3.2 sites for high and low force, respectively, and increased to 5.0 and 5.9 sites respectively after brushing. There was no significant difference with respect to incidence of abrasion. At baseline, 48 h. plaque levels were 2.2. The reduction in plaque scores with the low force was 60% and with the high force 56%. This difference was significant. With the oscillating rotating power toothbrush (Braun/Oral-B D17) the use of high force (+/-3.5 N) is less efficacious as compared to a regular low force (+/-1.5 N) while the incidence of gingival abrasion sites was comparable.


Monolithically mode division multiplexing photonic integrated circuit for large-capacity optical interconnection.
We propose and fabricate an on-chip mode division multiplexed (MDM) photonic interconnection system. Such a monolithically photonic integrated circuit (PIC) is composed of a grating coupler, two micro-ring modulators, mode multiplexer/demultiplexer, and two germanium photodetectors. The signals' generation, multiplexing, transmission, demultiplexing, and detection are successfully demonstrated on the same chip. Twenty Gb/s MDM signals are successfully processed with clear and open eye diagrams, validating the feasibility of the proposed circuit. The measured power penalties show a good performance of the MDM link. The proposed on-chip MDM system can be potentially used for large-capacity optical interconnection in future high-performance computers and big data centers.


USP2a protein deubiquitinates and stabilizes the circadian protein CRY1 in response to inflammatory signals.
The mammalian circadian clock coordinates various physiological activities with environmental cues to achieve optimal adaptation. The clock manifests oscillations of key clock proteins, which are under dynamic control at multiple post-translational levels. As a major post-translational regulator, the ubiquitination-dependent proteasome degradation system is counterbalanced by a large group of deubiquitin proteases with distinct substrate preference. Until now, whether deubiquitination by ubiquitin-specific proteases can regulate the clock protein stability and circadian pathways remains largely unclear. The mammalian clock protein, cryptochrome 1 (CRY1), is degraded via the FBXL3-mediated ubiquitination pathway, suggesting that it is also likely to be targeted by the deubiquitination pathway. Here, we identified that USP2a, a circadian-controlled deubiquitinating enzyme, interacts with CRY1 and enhances its protein stability via deubiquitination upon serum shock. Depletion of Usp2a by shRNA greatly enhances the ubiquitination of CRY1 and dampens the oscillation amplitude of the CRY1 protein during a circadian cycle. By stabilizing the CRY1 protein, USP2a represses the Per2 promoter activity as well as the endogenous Per2 gene expression. We also demonstrated that USP2a-dependent deubiquitination and stabilization of the CRY1 protein occur in the mouse liver. Interestingly, the pro-inflammatory cytokine, TNF-α, increases the CRY1 protein level and inhibits circadian gene expression in a USP2a-dependent fashion. Therefore, USP2a potentially mediates circadian disruption by suppressing the CRY1 degradation during inflammation.


Massive peptide sharing between viral and human proteomes.
Thirty viral proteomes were examined for amino acid sequence similarity to the human proteome, and, in parallel, a control of 30 sets of human proteins was analyzed for internal human overlapping. We find that all of the analyzed 30 viral proteomes, independently of their structural or pathogenic characteristics, present a high number of pentapeptide overlaps to the human proteome. Among the examined viruses, human T-lymphotropic virus 1, Rubella virus, and hepatitis C virus present the highest number of viral overlaps to the human proteome. The widespread and ample distribution of viral amino acid sequences through the human proteome indicates that viral and human proteins are formed of common peptide backbone units and suggests a fluid compositional chimerism in phylogenetic entities canonically classified distantly as viruses and Homo sapiens. Importantly, the massive viral to human peptide overlapping calls into question the possibility of a direct causal association between virus-host sharing of amino acid sequences and incitement to autoimmune reactions through molecular recognition of common motifs.


Unraveling City-Specific Microbial Signatures and Identifying Sample Origins for the Data From CAMDA 2020 Metagenomic Geolocation Challenge.
The composition of microbial communities has been known to be location-specific. Investigating the microbial composition across different cities enables us to unravel city-specific microbial signatures and further predict the origin of unknown samples. As part of the CAMDA 2020 Metagenomic Geolocation Challenge, MetaSUB provided the whole genome shotgun (WGS) metagenomics data from samples across 28 cities along with non-microbial city data for 23 of these cities. In our solution to this challenge, we implemented feature selection, normalization, clustering and three methods of machine learning to classify the cities based on their microbial compositions. Of the three methods, multilayer perceptron obtained the best performance with an error rate of 19.60% based on whether the correct city received the highest or second highest number of votes for the test data contained in the main dataset. We then trained the model to predict the origins of samples from the mystery dataset by including these samples with the additional group label of "mystery." The mystery dataset compromised of samples collected from a subset of the cities in the main dataset as well as samples collected from new cities. For samples from cities that belonged to the main dataset, error rates ranged from 18.18 to 72.7%. For samples from new cities that did not belong to the main dataset, 57.7% of the test samples could be correctly labeled as "mystery" samples. Furthermore, we also predicted some of the non-microbial features for the mystery samples from the cities that did not belong to main dataset to draw inferences and narrow the range of the possible sample origins using a multi-output multilayer perceptron algorithm.


Current Scientific Impact of Ss Cyril and Methodius University of Skopje, Republic of Macedonia in the Scopus Database (1960-2014).
The aim of this study was to analyze current scientific impact of Ss Cyril and Methodius University of Skopje, Republic of Macedonia in the Scopus Database (1960-2014). Affiliation search of the Scopus database was performed on November 23, 2014 in order to identify published papers from the Ss Cyril and Methodius University of Skopje (UC&M), Republic of Macedonia. A total number of 3960 articles (3055 articles from UC&M, 861 articles from Faculty of Medicine, UC&M, and 144 articles from Faculty of Pharmacy, UC&M) were selected for analysis (1960-2014). SCImago Journal Rank (SJR), Source Normalized Impact per Paper (SNIP) and h-index were calculated from the Scopus database. The number of published papers was sharply increased with maximum of 379 papers in 2012 year. The largest number of papers has been published in Macedonian Journal of Medical Sciences, Journal of Molecular Structure, Lecture Notes in Computer Science, Acta Pharmecutica, and Macedonian Journal of Chemistry and Chemical Engineering. The biggest SJR and SNIP has journal Nephrology Dialysis Transplantation. First three places of the top ten authors belong to Dimirovski GM, Gavrilovska L, and Gusev M. Top three places based on Scopus h-index (total number of published papers) belong to Kocarev L, Stafilov T, and Polenakovic M. The majority of papers originate from UC&M, but significant numbers of papers are affiliated to Faculty of Medicine, Faculty of Pharmacy, and Institute of Chemistry as members of UC&M, as well as Macedonian Academy of Sciences and Arts. Articles are the most dominant type of documents followed by conference papers, and review articles. Medicine is the most represented subject. Officials of the Ss Cyril and Methodius University of Skopje should undertake more effective and proactive policies for journal publishers and their Editorial Boards in order to include more journals from UC&M in the Scopus database.


Relationship of parent-child communication to child's exploratory behavior and self-differentiation.
In a study that investigated the relationship between patterns of acknowledgment in parent--child communication and the child's exploratory behavior and self-differentiation, subjects included 77 healthy perschool children between the ages of 3 years, 3 months and 4 years, 9 months and their mothers. Data on parent--child communication were collected in the home setting during a 30-minute observation in which mothers and children were engaged in a series of semi-structured play activities. Maternal responses to their children's assertions were coded as nonevaluative recognition, positive recognition, negative recognition, direction, or nonrecognition. A score on parent--child communication was the ratio of parental nonevaluative recognition and positive recognition combined to parental negative recognition, direction, and nonrecognition combined. Testing of the children on exploratory behavior and self-differentiation was done on an individual basis in their respective nursery schools. A low positive correlation (r = .237, p less than .05) between parent--child communication and children's self-differentiation was observed. Contrary to expectation, a slight negative correlation (r = -.101, p greater than .05) between parent--child communication and children's exploratory behavior was observed. Auxiliary analyses of the data, taking into consideration the child's sex, revealed that the negative relationship between parent--child-communication and children's exploratory behavior was characteristic of the mother-daughter dyads only (r = -.325, p = .08). A correlation of .078 (p greater than .05 was obtained for mother--son communication with boys' exploratory behavior.


Meta-analysis of QTLs associated with popping traits in maize (Zea mays L.).
The rising demand for popcorn necessitates improving the popping quality with higher yield of popcorn cultivars. Towards this direction several Quantitative Traits Loci (QTLs) for popping traits have been identified. However, identification of accurate and consistent QTLs across different genetic backgrounds and environments is necessary to effectively utilize the identified QTLs in marker-assisted breeding. In the current study, 99 QTLs related to popping traits reported in 8 different studies were assembled and projected on the reference map "Genetic 2005" using BioMercator v4.2 to identify metaQTLs with consistent QTLs. Total ten metaQTLs were identified on chromosome 1 (7 metaQTLs) and 6 (3 metaQTLs) with physical distance ranging between 0.43 and 12.75 Mb, respectively. Four identified metaQTLs, viz., mQTL1_1, mQTL1_5, mQTL1_7 and mQTL6_2 harboured 5-8 QTL clusters with moderately high R2 value. The clustered QTLs were from two or more experiments. Based on the expression pattern in endosperm and pericarp tissues, a total of 229 genes were selected. Nineteen of these genes are involved in carbohydrate metabolism. Of the 19 genes specifically involved in carbohydrate metabolism, 11 of them were in these regions, implying the importance of these clustered QTLs. MetaQTL1_1 at bin location 1.01 coincided with the reported QTLs related to various agronomic traits like stalk diameter, tassel length, leaf area and plant height. The identified metaQTLs can be further explored for fine mapping and candidate gene identification, which can be validated by loss or gain of function. Identified metaQTLs can be used for introgression of popping traits towards enhancing the popping ability.


Role of cytokine storm in coronavirus infections: culprit or accomplice?
At present, there are seven known types of human coronaviruses (HCoVs), which can be further divided into two categories: low pathogenic and highly pathogenic. The low pathogenic HCoVs infect the upper respiratory tract, mainly causing mild, cold-like respiratory diseases. By contrast, highly pathogenic HCoVs mainly infect the lower respiratory tract and cause fatal types of pneumonia, which include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as the recent outbreak of coronavirus disease 2019 (COVID-19). Highly pathogenic HCoV infection has a high morbidity and mortality, which is usually related to the strong immune response induced by highly proinflammatory cytokines, which is also known as "cytokine storm". Therefore, it is particularly important to explore the role of cytokine storm in the process of highly pathogenic HCoV infection. We review the epidemiological and clinical manifestations of highly pathogenic HCoV infection, and reveal the pathology of cytokine storm and its role in the process of highly pathogenic HCoV infection.


[The echocardiographic evaluation and its predicted prognosis of acute left cardiac systolic dysfunction in critically ill patients].
The purpose of this study was to evaluate the significance of echocardiography for the prognosis of acute left cardiac dysfunction in critically ill patients. A prospective cohort study was conducted in patients with acute left cardiac dysfunction in the Department of Critical Care Medicine, Peking Union Medical College Hospital from June 2013 to June 2014. Patients were divided into four groups according to the echocardiographic manifestation, including biventricular failure, left ventricular failure, coronary related segmental movement disorder, non-coronary related segmental movement disorder. All patients were treated with standard hemodynamic therapy. The duration of cardiotonic drug use, the period of mechanical ventilation, the length of ICU stay and 28-day mortality rate were recorded. A total of 132 patients were retrospectively enrolled in this study. The incidence of coronary heart disease in the coronary related segmental movement disorder group (88.0%, 22/25) was higher than that in the other three groups (P<0.001), while other general clinical information between groups at baseline was comparable (P>0.05). Sepsis or septic shock was the main cause of acute left cardiac systolic dysfunction. The 28-day mortality rate in biventricular failure group was 21.05%, 19.05% in left ventricular failure group, 20.00% in coronary related segmental movement disorder group, and 1/10 in non-coronary related segmental movement disorder group (P<0.001). However, the duration of cardiotonic drug use, the period of mechanical ventilation, and the length of ICU stay were similar in all groups (P>0.05) .In biventricular failure group, previous history of left ventricular diastolic dysfunction significantly worsened the 28-day mortality rate (5/7, P<0.001). while diastolic dysfunction did not affect cardiotonic drug use, the period of mechanical ventilation and length of ICU stay(P>0.05). The different echocardiographic features of acute left cardiac systolic dysfunction in critically ill patients predict the different prognosis. We need to setup an evaluation system including left cardiac systolic/diastolic function and right cardiac function, which may improve the process of workflow.


Star Excursion Balance Test as a predictor of lower extremity injury in high school basketball players.
Prospective cohort. To determine if Star Excursion Balance Test (SEBT) reach distance was associated with risk of lower extremity injury among high school basketball players. Although balance has been proposed as a risk factor for sports-related injury, few researchers have used a dynamic balance test to examine this relationship. Prior to the 2004 basketball season, the anterior, posteromedial, and posterolateral SEBT reach distances and limb lengths of 235 high school basketball players were measured bilaterally. The Athletic Health Care System Daily Injury Report was used to document time loss injuries. After normalizing for lower limb length, each reach distance, right/left reach distance difference, and composite reach distance were examined using odds ratio and logistic regression analyses. The reliability of the SEBT components ranged from 0.82 to 0.87 (ICC3,1) and was 0.99 for the measurement of limb length. Logistic regression models indicated that players with an anterior right/left reach distance difference greater than 4 cm were 2.5 times more likely to sustain a lower extremity injury (P<.05). Girls with a composite reach distance less than 94.0% of their limb length were 6.5 times more likely to have a lower extremity injury (P<.05). We found components of the SEBT to be reliable and predictive measures of lower extremity injury in high school basketball players. Our results suggest that the SEBT can be incorporated into preparticipation physical examinations to identify basketball players who are at increased risk for injury.


Activity of epirubicin and dibromodulcitol in advanced breast cancer. Results of the South-East European Oncology Group Study.
The therapeutic efficacy of the combination of epirubicin + dibromodulcitol was evaluated in 108 previously treated or untreated patients with advanced breast cancer. The overall response rate was 39.8%, complete remission 3.7% (mean duration 6.3 months) and partial remission 36.1% (mean duration 3.5 months). The response was rated in function of age, menopausal status, performance status and previous therapy. Toxicity (in case of 115 patients) was evaluated according to the WHO recommendation. The similar therapeutic effectiveness and less toxicity of the above drug combination compared to ADM + DBD regimen are demonstrated.


Population-based epidemiology, risk factors and screening of intraductal papillary mucinous neoplasm patients.
Intraductal papillary mucinous neoplasm (IPMN) was first recognized in the 1980s with increasing publications over the last decade as the incidence increased sharply, especially at tertiary-care referral centers. Population-based studies have estimated the age and sex-adjusted cumulative incidence of IPMN to be 2.04 per 100 000 person-years (95% confidence interval: 1.28-2.80). It is now understood that IPMN can be classified anywhere along the spectrum of the adenoma to carcinoma sequence and often harbors mutations in genes such as KRAS early in the disease process. Many patients are diagnosed incidentally after imaging of the abdomen for other diagnostic purposes. Patients that present with a history of symptoms such as pancreatitis and abdominal pain are at high risk of harboring a malignancy. Clinicopathologic features such as involvement of the main pancreatic duct, presence of mural nodules, and side branch disease > 3.0 cm in size may indicate that there is an underlying invasive component to the IPMN. In addition, the incidence of extra-pancreatic neoplasms is higher in patients with IPMN, with reported rates of 25% to 50%. There are no current screening recommendations to detect and diagnose IPMN but once the diagnosis is made, screening for extrapancreatic neoplasms such as colon polyps and colorectal cancer should be considered. Surgical resection is the recommend treatment for patients with high-risk features while close observation can be offered to patients without worrisome signs and symptoms of carcinoma.


Robust Nanocellulose/Metal-Organic Framework Aerogel Composites: Superior Performance for Static and Continuous Disposal of Chemical Warfare Agent Simulants.
Environment-friendly and robust nanocellulose/metal-organic framework aerogel composites were prepared for effective detoxification of chemical warfare agent simulants both in static and dynamic continuous flow systems. For this, we fabricated a durable porous composite of the UiO-66 catalyst and TEMPO-oxidized cellulose nanofibers (TOCN) to examine as a detoxification filter. Even with over 50 wt % UiO-66, the obtained cellulose aerogel composites exhibited high stability without leaking of UiO-66 for 4 weeks under an aqueous state. The cellulose aerogel composite with 54 wt % UiO-66 showed a quite high surface area (483 m2 g-1) despite the presence of TOCN, which caused fast degradation of methyl paraoxon (MPO), a nerve agent simulant, with a 0.7 min half-life in an aqueous solution with N-ethylmorpholine buffer. This aerogel composite was then examined as the detoxification filter in the continuous flow system under a 7.2 mL h-1 flow rate, which surprisingly decomposed 53.7 g of MPO within 1 h with 1 m2 of the effective area.


Mouse Ovary Cryopreservation.
Ovary cryopreservation in combination with orthotopic ovary transplantation can produce live offspring and complement embryo and sperm cryopreservation programs. One method for ovary cryopreservation is described here.


Andrenergic reactivity of the gastro-intestinal tract. I. Fundus of the rat's stomach.
The adrenergic receptors of the fundus of rat stomach are both type alpha and type beta. Activation of the alpha-adrenergic receptors gives a diphasic response in which inhibition precedes excitation. The beta-adrenergic receptors mediate exclusively inhibitory response; the beta-adrenergic component of the inhibitory response is clearly observed only when the alpha-adrenergic component is diminished. The beta-receptors can be assigned, with some reserve, to the betaalpha group.


[Clinical analysis for the treatment of 63 cases of orbital tumors in Xinjiang].
To analyse the clinical features, histopathological classifications, treatments and prognosis of orbital tumors in Xinjiang. The authors retrospectively analyse 63 patients (64 eyes) with orbital tumors, including all nationalities which had been received and treated in ophthalmic department of the PLA 474th Hospital during 2005 to 2009. The nationality composition in our cases was 37 Han, 16 Uygur (16 eyes), 4 Hui, 3 Mongol, and 3 Kazak. Our data mainly consisted of benign tumor., in which, the majority were the vascular tumors, and then were cysts, inflammatory pseudotumor, neurogenic tumors, mixed tumors of lacrimal gland, lipoma and hydatid. The malignant tumors mainly consisted of rhabdomyosarcoma and adenocarcinoma of lacrimal gland, then was non-Hodgkin lymphoma. The operation methods we selected were approaching by orbital skin or anterior skin incision, lateral orbitotomy and approaching by outer canthus incision plus lower fornical conjunctiva incision. The severe postoperative complication was impaired vision, and 2 patients with inflammatory pseudotumor had recrudesced. There is no difference on the types and morbidity situation of orbital tumors between Xinjiang and other areas in general, in addition orbital hydatid which was closely related to regional characteristic of Xinjiang, Surgical excision is the main and effective treatment, the prognosis is related to the local tissue extension of tumor, comprehensive pre-operation preparations, careful operation, appropriate post-operative managements and rich clinic experience of doctor.


Changing molecular epidemiology of methicillin-resistant Staphylococcus aureus in a small geographic area over an eight-year period.
The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) at an international level shows that most MRSA strains belong to a few pandemic clones. At the local level, a predominance of one or two clones was generally reported. However, the situation is evolving and new clones are emerging worldwide, some of them with specific biological characteristics, such as the presence of Panton-Valentine leucocidin (PVL). Understanding these changes at the local and international levels is of great importance. Our objective was to analyze the evolution of MRSA epidemiology at multiple sites on a local level (Western Switzerland) over a period of 8 years. Data were based on MRSA reports from seven sentinel laboratories and infection control programs covering different areas. Pulsed-field gel electrophoresis was used to type MRSA isolates. From 1997 to 2004, a total of 2,256 patients with MRSA were reported. Results showed the presence of four predominant clones (accounting for 86% of patients), which could be related to known international clones (Berlin, New York/Japan, Southern Germany, and Iberian clones). Within the small geographic region, the 8-year follow-up period in the different areas showed spacio-temporal differences in the relative proportions of the four clones. Other international MRSA clones, as well as clones showing genetic characteristics identical to those of community-acquired MRSA (SCCmec type IV and the presence of PVL genes), were also identified but presumably did not disseminate. Despite the worldwide predominance of a few MRSA clones, our data showed that at a local level, the epidemiology of MRSA might be different from one hospital to another. Moreover, MRSA clones were replaced by other emerging clones, suggesting a rapid change.


Successful therapy of Niemann-Pick disease by implantation of human amniotic membrane.
In a patient with a lysosomal storage disorder, not involving the CNS, repeated implantations of human amniotic sheets have proved to provide a successful approach to enzyme replacement therapy. Implantation of pure epithelial cells, separated from the other cell types of the amnion, might markedly improve the procedure, avoiding some risks of host-versus-graft rejection.


Gastric and duodenal polyps in familial adenomatous polyposis: a prospective study of the nature and prevalence of upper gastrointestinal polyps.
One hundred patients with familial adenomatous polyposis have prospectively undergone gastroduodenoscopy to identify and characterise polyps found. Forty six patients had polyps in the stomach or duodenum. Thirty five patients had adenomas (33 in duodenum, two in stomach) and 26 patients had fundic gland polyps. Some of these patients had polyps in the stomach and the duodenum. Adenomas in the duodenum were present in 33% of patients studied with Gardner's syndrome variant (p = 0.04). Adenomas were also more common in older patients. As adenomas may be a precursor of adenocarcinoma, routine surveillance of the stomach and duodenum with gastroduodenoscopy is recommended in patients affected with familial adenomatous polyposis.


Can changes in resistance exercise workload influence internal load, countermovement jump performance and the endocrine response?
This study examined the influence of differing volume load and intensity (%1 repetition maximum[%1RM]) resistance exercise workouts on session rating of perceived exertion (sRPE) countermovement jump (CMJ) performance and endocrine responses. Twelve participants performed a workout comprising four exercises (bench press, back squat, deadlift and prone bench pull) in randomised order as either power (POW); 3 sets × 6 repetitions at 45%1RM × 3 min inter-set rest, strength (ST); 3 sets × 3 repetitions at 90%1RM × 3 min inter-set rest, or hypertrophy (HYP); 3 sets × 10 repetitions at 70%1RM × 1 min inter-set rest in a randomised-crossover design. CMJ performance and endocrine responses were measured immediately pre-, post-, 12, 24, 48 and 72 h post-exercise. POW sRPE (3.0 ± 1.0) was lower than ST (4.5 ± 1.0) (P = 0.01), and both were lower than HYP (8.5 ± 1.0) (P = 0.01). Duration of CMJ decrement was longer (P ≤ 0.05) for HYP (72 h) compared to POW (12 h) and ST (24 h). Testosterone concentration was greater (P ≤ 0.05) immediately post-exercise in HYP compared to POW and ST. In conclusion, less inter-set rest, greater volume load and intensity (%1RM) may increase sRPE, duration of CMJ performance decrement and testosterone responses in resistance exercise.


Real-time fMRI brain-computer interface: development of a "motivational feedback" subsystem for the regulation of visual cue reactivity.
Here we present a novel neurofeedback subsystem for the presentation of motivationally relevant visual feedback during the self-regulation of functional brain activation. Our "motivational neurofeedback" approach uses functional magnetic resonance imaging (fMRI) signals elicited by visual cues (pictures) and related to motivational processes such as craving or hunger. The visual feedback subsystem provides simultaneous feedback through these images as their size corresponds to the magnitude of fMRI signal change from a target brain area. During self-regulation of cue-evoked brain responses, decreases and increases in picture size thus provide real motivational consequences in terms of cue approach vs. cue avoidance, which increases face validity of the approach in applied settings. Further, the outlined approach comprises of neurofeedback (regulation) and "mirror" runs that allow to control for non-specific and task-unrelated effects, such as habituation or neural adaptation. The approach was implemented in the Python programming language. Pilot data from 10 volunteers showed that participants were able to successfully down-regulate individually defined target areas, demonstrating feasibility of the approach. The newly developed visual feedback subsystem can be integrated into protocols for imaging-based brain-computer interfaces (BCI) and may facilitate neurofeedback research and applications into healthy and dysfunctional motivational processes, such as food craving or addiction.


Microsurgical Management of a Marginal Sinus Dural Arteriovenous Fistula: 2-Dimensional Operative Video.
Dural arteriovenous fistulas (DAVFs) are benign but may present with life-threatening hemorrhage or symptoms of venous hypertension (eg, progressive myelopathy).1-3 DAVFs follow well-described anatomic patterns.4 The marginal sinus is located between the layers of the dura, circumferentially around the foramen magnum. It communicates with the basal venous plexus of the clivus anteriorly and the occipital sinus posteriorly.5,6 Arterial supply to the dura in this region that fistulizes into the sinus arises from meningeal branches from the V3 or V4 segments. A man in his early 70s presented with chronic neck pain and new onset of left arm and face paresthesias. He had brisk patellar reflexes bilaterally and a marginal sinus DAVF, with numerous dilated veins around the cisterna magna, causing dorsal cervicomedullary compression. Angiography confirmed the diagnosis of DAVF rather than arteriovenous malformation. Endovascular embolization was considered, but surgery was preferable because of poor transarterial access. The patient underwent left far lateral craniotomy and C1 laminectomy with exposure of the condylar fossa. The dura was carefully elevated laterally, revealing a network of dilated tortuous veins, with multiple points of fistulous connection within the dura emanating in a large venous varix. Indocyanine green videoangiography showed the aberrant flow dynamics. The fistulous point was occluded with aneurysm clips on the venous side, then cauterized and interrupted. The patient was discharged within 3 d of surgery and had full resolution of symptoms at 6 wk. Angiography confirmed complete obliteration of the DAVF. The patient provided written informed consent for treatment. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.


Ginkgolide A targets forkhead box O1 to protect against lipopolysaccharide-induced septic cardiomyopathy.
Ginkgolide A (GA), a main terpenoid extracted from Ginkgo biloba, possesses biological activities such as anti-inflammatory, anti-tumor, and liver protection. However, the inhibitory effects of GA on septic cardiomyopathy remain unclear. This study aimed to explore the effects and mechanisms of GA in countering sepsis-induced cardiac dysfunction and injury. In lipopolysaccharide (LPS)-induced mouse model, GA alleviated mitochondrial injury and cardiac dysfunction. GA also significantly reduced the production of inflammatory and apoptotic cells, the release of inflammatory indicators, and the expression of oxidative stress-associated and apoptosis-associated markers, but increased the expression of pivotal antioxidant enzymes in hearts from LPS group. These results were consistent with those of in vitro experiments based on H9C2 cells. Database analysis and molecular docking suggested that FoxO1 was targeted by GA, as shown by stable hydrogen bonds formed between GA with SER-39 and ASN-29 of FoxO1. GA reversed LPS-induced downregulation of nucleus FoxO1 and upregulation of p-FoxO1 in H9C2 cells. FoxO1 knockdown abolished the protective properties of GA in vitro. KLF15, TXN2, NOTCH1, and XBP1, as the downstream genes of FoxO1, also exerted protective effects. We concluded that GA could alleviate LPS-induced septic cardiomyopathy via binding to FoxO1 to attenuate cardiomyocyte inflammation, oxidative stress, and apoptosis.


Pulmonary Arterial Hypertension and Insulin Resistance.
The clinical recognition of pulmonary arterial hypertension (PAH) is increasing, and with recent therapeutic advances, short-term survival has improved. In spite of these advances, however, PAH remains a disease with substantial morbidity and long-term mortality. The pathogenesis of PAH involves a complex interaction of local and distant cytokines, growth factors, co-factors, and transcription factors occurring in the right genetic and environmental setting. These factors ultimately lead to the detrimental changes in vascular anatomy and function seen in PAH patients. An important association between obesity/insulin resistance and PAH has recently been identified. Both conditions occur in the presence of a chronic low-grade inflammatory state, and although it is unlikely that a single pathway is solely responsible for the observed association, deficiencies in adiponectin, apolipoprotein E (ApoE) and peroxisome proliferator-activator receptor gamma (PPAR-γ) activity likely play a prominent role. Although incompletely understood, it is clear that further investigation is warranted and the role of weight loss and improved glycemic control in the treatment of at-risk patients with PAH and obesity should be determined.


Exogenous siRNAs against chitin synthase gene suppress the growth of the pathogenic fungus Macrophomina phaseolina.
Macrophomina phaseolina, causative agent of the charcoal rot disease, impacts over 500 plant species, causing devastating crop failures worldwide. Due to the lack of effective management approach, charcoal rot can result in serious loss, especially during years with hot and dry summers. This study aims to evaluate the effectiveness of using the RNA interference (RNAi) mechanism to suppress the growth of M. phaseolina, through exogenous application of small interfering RNA (siRNA) targeting one of the chitin synthase (MpCHS) genes in the M. phaseolina genome. Since chitin is one of the main components in the fungal cell wall, we hypothesize that suppressing the expression of MpCHS through RNAi will negatively affect the growth of the fungus, which may result in reduced virulence toward the host. Of the seven candidate MpCHS genes assessed, MpCHS6 showed consistent expression in plate-grown fungus and in infected plant tissue and was chosen as the target for RNAi knockdown. Two siRNAs were designed to target MpCHS6 and tested through in vitro application in M. phaseolina culture. Both siRNAs suppressed growth of the fungus at multiple time points and under varied environmental conditions. More importantly, the growth suppression was well correlated with down-regulation of the MpCHS6 gene. These results indicate that exogenous siRNAs can suppress gene expression in M. phaseolina even when applied in vitro. In addition, targeting a MpCHS gene may provide an effective way to control the fungal growth. Our study provides firsthand knowledge on RNAi in M. phaseolina, which benefits not only basic research that focuses on understanding gene function in this species but also application of RNAi-based technology in disease control in the future.


Role of aquaporin-7 in ghrelin- and GLP-1-induced improvement of pancreatic β-cell function after sleeve gastrectomy in obese rats.
Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues as well as for pancreatic insulin secretion. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in β-cells, and AQP12, an aquaporin related to pancreatic damage, in the improvement of pancreatic function and steatosis after sleeve gastrectomy in diet-induced obese rats. Male Wistar obese rats (n=125) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by sleeve-gastrectomized animals) interventions. The tissue distribution and expression of AQPs in the rat pancreas were analyzed by real-time PCR, western blotting and immunohistochemistry. The effect of ghrelin isoforms and glucagon-like peptide 1 (GLP-1) on insulin secretion, triacylglycerol (TG) accumulation and AQP expression was determined in vitro in RIN-m5F β-cells. Sleeve gastrectomy reduced pancreatic β-cell apoptosis, steatosis and insulin secretion. Lower ghrelin and higher GLP-1 concentrations were also found after bariatric surgery. Acylated and desacyl ghrelin increased TG content, whereas GLP-1 increased insulin release in RIN-m5F β-cells. Sleeve gastrectomy was associated with an upregulation of AQP7 together with a normalization of the increased AQP12 levels in the rat pancreas. Interestingly, ghrelin and GLP-1 repressed AQP7 and AQP12 expression in RIN-m5F β-cells. AQP7 protein was negatively correlated with intracellular lipid accumulation in acylated ghrelin-treated cells and with insulin release in GLP-1-stimulated β-cells. AQP7 upregulation in β-cells after sleeve gastrectomy contributes, in part, to the improvement of pancreatic steatosis and insulin secretion by increasing intracellular glycerol used for insulin release triggered by GLP-1 rather than for ghrelin-induced TG biosynthesis.


Does Perceived Green Space Quality Matter? Linking Norwegian Adult Perspectives on Perceived Quality to Motivation and Frequency of Visits.
Individual perceptions of green space quality are essential when a user considers engaging in activities. This national-scale study provides insights into Norwegians' quality perceptions of municipal green space, visit frequency and motivations for engaging in different activities. We applied regression analysis to investigate how various factors affect the outcome variables, quality perceptions and visit frequency from a sample of the Norwegian adult population. Results reveal that Norwegians perceive their green spaces as having good quality, and higher quality perceptions have a positive influence on green space visits. Half of the respondents visited green spaces out of intrinsic motives in high-quality environments providing fresh air, experiences of nature and quietness. It is essential, however, to take into account that less reported activity mirrors groups of respondents who least often visit green spaces.


Branched tellurium hollow nanofibers by galvanic displacement reaction and their sensing performance toward nitrogen dioxide.
Electrospinning and galvanic displacement reaction were combined to synthesize ultra-long hollow tellurium (Te) nanofibers with controlled dimensions, morphology and crystallinity by simply tailoring the electrolyte concentration applied. Within different morphologies of nanofibers, the branched Te nanostructure shows the greatest sensing performance towards NO2 at room temperature.


The Cooking and Pneumonia Study (CAPS) in Malawi: A Nested Pilot of Photovoice Participatory Research Methodology.
The Cooking and Pneumonia Study (CAPS) is a village-level randomised controlled trial of an advanced cookstove intervention to prevent pneumonia in children under the age of 5 in rural Malawi (www.capstudy.org). The trial offers a unique opportunity to gain understanding about the social and cultural factors that may facilitate sustained use of improved cookstoves. In January 2015, the use of Photovoice as a participatory research methodology was piloted at the CAPS Chikhwawa site. Photovoice is a photographic technique that allows communities (including women and marginalised groups) to share knowledge about their perspectives and priorities. Four households were given digital cameras and asked to collect images over 24-48 hours and were then interviewed on film about their selection. This resulted in over 400 images and a one hour long film that revealed community concerns and could be thematically analysed. The collection of interview data through film was useful for capturing discussion and was acceptable to participants. Photovoice is a feasible participatory research methodology that can play a valuable role in qualitative studies of improved cookstove adoption in challenging resource poor settings.


Up/down anisotropies of vertical saccades in healthy children from 6 to 10 years of age.
Although the overall development of saccades in children has recently gained increasing interest, the precise characteristics of vertical saccades remain understudied. This study focused on the development of vertical saccades and their interaction with vergence movements. Thirty-one children (mean age: 7.33 ± 0.21 years) performed vertical saccades with an eccentricity of 7.5° at 40 and 150 cm viewing distance, in a simultaneous paradigm (simultaneous offset of central dot and onset of peripheral target). The results revealed shorter latency, more vertical conjugate postsaccadic drift after upward saccades, and less horizontal vergence during and after upward saccades in children. Furthermore, the intrasaccadic convergence decreased progressively with children's age for upward saccades. Relative to adult behavior, children present more hypometric saccades, longer latencies, higher vertical disconjugacy, and a different pattern of horizontal vergence during vertical saccades. This result suggests that up/down asymmetries are built progressively in mutual interaction with a perceptive peripheral bias such as up being perceived as far and down as near.


Estimating segment inertial parameters using fan-beam DXA.
Body segment inertial parameters are required as input parameters when the kinetics of human motion is to be analyzed. However, owing to interindividual differences in body composition, noninvasive inertial estimates are problematic. Dual-energy x-ray absorptiometry (DXA) is a relatively new imaging approach that can provide cost- and time-effective means for estimating these parameters with minimal exposure to radiation. With the introduction of a new generation of DXA machines, utilizing a fan-beam configuration, this study examined their accuracy as well as a new interpolative data-reduction process for estimating inertial parameters. Specifically, the inertial estimates of two objects (an ultra-high molecular density plastic rod and an animal specimen) and 50 participants were obtained. Results showed that the fan-beam DXA, along with the new interpolative data-reduction process, provided highly accurate estimates (0.10-0.39%). A greater variance was observed in the center of mass location and moment of inertia estimates, likely as a result of the course end-point location (1.31 cm). However, using a midpoint interpolation of the end-point locations, errors in the estimates were greatly reduced for the center of mass location (0.64-0.92%) and moments of inertia (-0.23 to -0.48%).


All the observed universe has contributed to life.
This paper presents evidence that virtually all electrons and nuclei of the atoms that are or have been part of living matter on Earth came from almost all stars in our and nearby galaxies and even from all other galaxies in the Universe that have produced observed high-energy gamma rays. However, a standard 70 kg human is always making about 7 3He, 600 40Ca, and 3000 14N nuclei every second by radioactive decay of 3H, 40K, and 14C, respectively.


Transdermal cellular membrane penetration of proteins with gold nanoparticles: a molecular dynamics study.
Transdermal delivery, where the skin acts as the route for local or systemic distribution, presents a lot of advantages over conventional routes such as oral and intravenous and intramuscular injections. However, the delivery of large biomolecules like proteins through the skin is challenging due to their size and structural properties. A molecular level understanding of their transport across the skin barrier is desirable to design successful formulations. We have employed constrained and unconstrained coarse grained molecular dynamics simulation techniques to obtain the molecular mechanism of penetration of the horseradish peroxidase (HRP) protein into the skin, in the presence and absence of gold nanoparticles (AuNPs). Unconstrained simulations show that HRP, when considered individually, was not able to breach the skin barrier, while in the presence of AuNPs, it first binds to the AuNPs and then breaches the barrier. The constrained simulations revealed that there was a free energy barrier for HRP to permeate inside the skin lipid layer when taken alone, while in the presence of gold nanoparticles, no barrier was found. Our study opens up the field of computational modeling based design of nanoparticle carriers for a given protein's transdermal delivery.


Percutaneous retrogasserian glycerol rhizotomy for tic douloureux: Part 2. Results nd implications of trigeminal evoked potential studies.
Trigeminal evoked potentials were recorded before and 6 weeks after a percutaneous retrogasserian glycerol rhizotomy was performed in 22 patients with tic douloureux. The latency of the trigeminal evoked potential (TEP) N20 peak and the sensory threshold to electrical stimulation of the maxillary gum were measured in each patient. The N20 latency differences between normal and affected sides for each patient were reduced after glycerol injection. Sensory thresholds were significantly different between the normal and the affected sides both before and after rhizotomy. These results were interpreted to indicate that glycerol more specifically affects the damaged myelinated axons implicated in the pathogenesis of trigeminal neuralgia. Of the 22 patients, 82% were either pain-free or significantly improved after operation. Postoperative normal N20 latencies were associated with pain relief in most cases. Our preliminary experience suggests that recurrent pain is more likely to develop in those patients whose postoperative TEP remains abnormal, especially if the abnormality cannot be ascribed to a prior surgical deafferentiation procedure. In addition to providing insight into the mechanism of pain relief, TEP measurements may help to predict the likelihood of long term relief after percutaneous retrogasserian glycerol rhizotomy.


Socio-demographic determinants of participation in mammography screening.
Our objective was to use individual data on socio-demographic characteristics to identify predictors of participation in mammography screening and control to what extent they can explain the regional difference. We used data from mammography screening programmes in Copenhagen, 1991-1999, and Funen, 1993-2001, Denmark. Target groups were identified from the Population Register, screening data came from the health authority, and socio-demographic data from Statistics Denmark. Included were women eligible for at least 3 screens. The crude RR of never use versus always use was 3.21 (95%CI, 3.07-3.35) for Copenhagen versus Funen, and the adjusted RR was 2.55 (95%CI, 2.43-2.67). The adjusted RR for never use among women without contact to a primary care physician was 2.50 (95% CI, 2.31-2.71) and 2.89 (95% CI, 2.66-3.14), and for women without dental care 2.94 (95% CI, 2.77-3.12) and 2.88 (95% CI, 2.68-3.10) for Copenhagen and Funen, respectively. Other important predictive factors for nonparticipation were not being married and not being Danish. In conclusion, to enhance participation in mammography screening programmes special attention needs to be given to women not using other primary health care services. All women in Copenhagen, irrespective of their socio-demographic characteristics, had low participation. Screening programmes have to find ways to handle this urbanity factor.


Cation selectivity and inhibition of malignant glioma Na+ channels by Psalmotoxin 1.
Psalmotoxin 1 (a component of the venom of a West Indies tarantula) is a 40-amino acid peptide that inhibits cation currents mediated by acid-sensing ion channels (ASIC). In this study we performed electrophysiological experiments to test the hypothesis that Psalmotoxin 1 (PcTX1) inhibits Na+ currents in high-grade human astrocytoma cells (glioblastoma multiforme, or GBM). In whole cell patch-clamped cultured GBM cells, the peptide toxin quickly and reversibly inhibited both inward and outward current with an IC50 of 36 +/- 2 pM. The same inhibition was observed in freshly resected GBM cells. However, when the same experiment was performed on normal human astrocytes, the toxin failed to inhibit the whole cell current. We also determined a cationic selectivity sequence for inward currents in three cultured GBM cell lines (SK-MG-1, U87-MG, and U251-MG). The selectivity sequence yielded a unique biophysical fingerprint with inward K+ conductance approximately fourfold greater than that of Na+, Li+, and Ca2+. These observations suggest that PcTX1 may prove useful in determining whether GBM cells express a specific ASIC-containing ion channel type that can serve as a target for both diagnostic and therapeutic treatments of aggressive malignant gliomas.


A study on blood lipid profiles, aluminum and mercury levels in college students.
College students are in a period of transition from adolescence to adulthood, in which proper dietary habits and balanced nutritional intake are very important. However, improper dietary habits and lifestyles can bring several health problems. This study was performed to investigate blood lipid profiles, blood aluminum and mercury in college students and the relationships among them. The subjects were 80 college students (43 males and 37 females) in Gyeonggi-do. General characteristics, anthropometric measurements, blood pressure, blood lipids, SGOT, SGPT, and blood aluminum and mercury of the subjects were measured and analyzed, and their relationship was studied. The BMI was significantly higher in males, 23.69 ± 3.20 kg/m(2), than in females, 20.38 ± 2.37 kg/m(2) (P < 0.001). The blood pressure was significantly higher in males with 128.93 ± 12.92 mmHg systolic pressure and 77.14 ± 10.31 mmHg diastolic pressure compared to females with 109.78 ± 11.97 mmHg and 65.95 ± 6.92 mmHg, respectively (P < 0.001). HDL cholesterol in males, 61.88 ± 13.06 mg/dl, was lower than 64.73 ± 12.16 mg/dl in females, but other blood lipid levels were higher in males. Blood aluminum was significantly higher in males, 9.12 ± 2.11 µg/L, than in females, 8.03 ± 2.14 µg/L (P < 0.05), and blood mercury was higher in males, 3.08 ± 1.55 µg/L, than in females, 2.64 ± 1.49 µg/L. The blood lipids showed positive correlation with obesity and blood pressure. The degree of obesity, blood pressure, triglycerides, and LDL cholesterol were higher in males, suggesting possible association with chronic disease incidence such as hyperlipidemia and hypertension. Thus, it is considered that a systematic health education is needed for college students, especially for males.


Faecal microbiota composition is related to response to CDK4/6-inhibitors in metastatic breast cancer: A prospective cross-sectional exploratory study.
Cyclin-dependent kinase (CDK)4/6-inhibitors with endocrine therapy represent the standard of treatment of hormone receptor-positive(HR+)/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Gut microbiota seems to predict treatment response in several tumour types, being directly implied in chemotherapy resistance and development of adverse effects. No evidence is available on gut microbiota impact on efficacy of HR+ breast cancer treatment. We assessed the potential association among faecal microbiota and therapeutic efficacy of CDK4/6-inhibitors on 14 MBC patients classified as responders (R) and non-responders (NR) according to progression-free survival. A stool sample was collected at baseline and V3-V4 16S targeted sequencing was employed to assess its bacterial composition. Statistical associations with R and NR were studied. No significant differences were observed between R and NR in terms of α-/β-diversity at the phylum and species level. Machine-learning (ML) algorithms evidenced four bacterial species as a discriminant for R (Bifidobacterium longum, Ruminococcus callidus) and NR (Clostridium innocuum, Schaalia odontolytica), and an area under curve (AUC) of 0.946 after Random Forest modelling. Network analysis evidenced two major clusters of bacterial species, named Species Interacting Groups (SIG)1-2, with SIG1 harbouring 75% of NR-related bacterial species, and SIG2 regrouping 76% of R-related species (p < 0.001). Cross-correlations among several patients' circulating immune cells or biomarkers and bacterial species' relative abundances showed associations with potential prognostic implications. Our results provide initial insights into the gut microbiota involvement in sensitivity and/or resistance to CDK4/6-inhibitors + endocrine therapy in MBC. If confirmed in larger trials, several microbiota manipulation strategies might be hypothesised to improve response to CDK4/6-inhibitors.


Simultaneously Antimicrobial, Protein-repellent and Cell-compatible Polyzwitterion Networks: More Insight on Bioactivity and Physical Properties.
A poly(oxanorbornene)-based polyzwitterion with primary ammonium and carboxylate groups (PZI) has been reported previously as the first simultaneously antimicrobial and protein-repellent polyzwitterion. Here, additional physical and biological properties of three poly(oxanorbornene)-based polyzwitterions with different functional groups (PZI, the polycarboxybetaine PCB, and the polysulfobetaine PSB) are compared to understand the molecular origins of this unusual bioactivity. Additionally, the three polyzwitterions and the antimicrobial, polycationic SMAMP are exposed to proteins, bacteria suspensions, human plasma and serum. These interactions are investigated by surface plasmon resonance spectroscopy. In protein adhesion studies, neither fibrinogen nor lysozyme adhere irreversibly to PZI, yet reversible interaction with lysozyme is observed at pH 7 and 8. In the presence of bivalent cations, reversible fibrinogen adhesion on PZI and PSB is observed, but not on PCB. This might explain why mammalian cells grow on PZI and PSB, but not on PCB. PZI does not show human plasma adhesion, while PCB and PSB have 0.27 and 0.48 ng mm-2 adhered plasma, and SMAMP even 6.3 ng mm-2. Both PZI and SMAMP show strong serum adhesion, while no serum adhered to PCB, and only little to PSB. This could be related to the pH difference between serum and plasma, to which the pH-responsive primary ammonium groups are susceptible, while the permanently charged NR4 + groups are unaffected. Both PZI and PCB showed none or only little bacterial adhesion. PCB is also intrinsically antimicrobial against E. coli and S. aureus bacteria and thus is also simultaneously protein-repellent and antimicrobially active. Thus, while the carboxylate groups of PZI and PCB seems to be a prerequisite for the dual antimicrobial activity and protein-repellency, the pH-responsiveness of the primary ammonium group seems to make the PZI molecule vulnerable for protein adhesion in fluids that are slightly out of the physiological range.


Cell-type-specific expression of murine multifunctional galectin-3 and its association with follicular atresia/luteolysis in contrast to pro-apoptotic galectins-1 and -7.
Galectin-3 is a multifunctional protein with modular design. A distinct expression profile was determined in various murine organs when set into relation to homodimeric galectins-1 and -7. Fittingly, the signature of putative transcription-factor-binding sites in the promoter region of the galectin-3 gene affords a toolbox for a complex combinatorial regulation, distinct from the respective sequence stretches in galectins-1 and -7. A striking example for cell-type specificity was the ovary, where these two lectins were confined to the surface epithelium. Immunohistochemically, galectin-3 was found in macrophages of the cortical interstitium between developing follicles and medullary interstitium, matching the distribution of the F4/80 antigen. With respect to atresia and luteolysis strong signals in granulosa cells of atretic preantral but not antral follicles and increasing positivity in corpora lutea upon regression coincided with DNA fragmentation. Labeled galectin-3 revealed lactose-inhibitable binding to granulosa cells. Also, slender processes of vital granulosa cells which extended into the zona pellucida were positive. This study demonstrates cell-type specificity and cycle-associated regulation for galectin-3 with increased presence in atretic preantral follicles and in late stages of luteolysis.


Separation of Small-Diameter Single-Walled Carbon Nanotubes in One to Three Steps with Aqueous Two-Phase Extraction.
An aqueous two-phase extraction (ATPE) technique capable of separating small-diameter single-walled carbon nanotubes in one, two, or at the most three steps is presented. Separation is performed in the well-studied two-phase system containing polyethylene glycol and dextran, but it is achieved without changing the global concentration or ratio of cosurfactants. Instead, the technique is reliant upon the different surfactant shell around each nanotube diameter at a fixed surfactant concentration. The methodology to obtain a single set of surfactant conditions is provided, and strategies to optimize these for other diameter regimes are discussed. In total, 11 different chiralities in the diameter range 0.69-0.91 nm are separated. These include semiconducting and both armchair and nonarmchair metallic nanotube species. Titration of cosurfactant suspensions reveal separation to be driven by the pH of the suspension with each ( n, m) species partitioning at a fixed pH. This allows for an ( n, m) separation approach to be presented that is as simple as pipetting known volumes of acid into the ATPE system.


A Di-Copper-Peptoid in a Noninnocent Borate Buffer as a Fast Electrocatalyst for Homogeneous Water Oxidation with Low Overpotential.
Water electrolysis is a promising approach toward low-cost renewable fuels; however, the high overpotential and slow kinetics limit its applicability. Studies suggest that either dinuclear copper (Cu) centers or the use of borate buffer can lead to efficient catalysis. We previously demonstrated the ability of peptoids-N-substituted glycine oligomers-to stabilize high-oxidation-state metal ions and to form self-assembled di-copper-peptoid complexes. Capitalizing on these features herein we report on a unique Cu-peptoid duplex, Cu2(BEE)2, that is a fast and stable homogeneous electrocatalyst for water oxidation in borate buffer at pH 9.35, with low overpotential and a high turnover frequency of 129 s-1 (peak current measurements) or 5503 s-1 (FOWA); both are the highest reported for Cu-based water electrocatalysts to date. BEE is a peptoid trimer having one 2,2'-bipyridine ligand and two ethanolic groups, easily synthesized on solid support. Cu2(BEE)2 was characterized by single-crystal X-ray diffraction and various spectroscopic and electrochemical techniques, demonstrating its ability to maintain stable in four cycles of controlled potential electrolysis, leading to a high overall turnover number of 51.4 in a total of 2 h. Interestingly, the catalytic activity of control complexes having only one ethanolic side chain is 2 orders of magnitude lower than that of Cu2(BEE)2. On the basis of this comparison and on mechanistic studies, we propose that the ethanolic side chains and the borate buffer have significant roles in the high stability and catalytic activity of Cu2(BEE)2; the -OH groups facilitate protons transfer, while the borate species enables oxygen transfer toward O-O bond formation.


Dane particle-associated DNA polymerase and e antigen: relation to chronic hepatitis among carriers of hepatitis B surface antigen.
Thirty-nine carriers of hepatitis B surface antigen (HBs Ag) were studied with respect to e antigen and Dane particle-associated DNA polymerase activity and their relation to chronic hepatitis. Most of these individuals were followed for four or five years. A strong correlation between e antigen and DNA polymerase activity was found. Of the 22 e antigen-positive patients, 21 showed polymerase activity; none of the 13 e antigen-negative patients (one of whom had antibody to e antigen) had such activity. Three of four patients who became e antigen-negative after being e antigen-positive showed loss of polymerase activity. An independent clinical evaluation showed a strong correlation between chronic hepatitis and positive reactions in the tests for e antigen and DNA polymerase. The results emphasize the possibility of differentiating between groups of chronic carriers of HBs Ag by testing for e antigen and Dane particle-associated DNA polymerase activity. The differentiation may have important clinical implications.


Inter- and intra-city comparisons of PM2.5 concentration changes under COVID-19 social distancing in seven major cities of South Korea.
The COVID-19 pandemic has prompted governments around the world to impose mitigation strategies of unprecedented scales, typically involving some form of restrictions on social activities and transportation. The South Korean government has been recommending a collection of guidelines now known as social distancing, leading to reduced human activities. This study analyzes changes in the concentrations of fine particulate matter (PM2.5) during the 30-day periods before and since the start of social distancing on 29 February 2020 using measurement data from air quality monitoring stations at various locations of the seven major cities of South Korea, namely, Seoul, Busan, Incheon, Daegu, Daejeon, Gwangju, and Ulsan. All seven cities experienced decreased levels of PM2.5 concentration by up to 25% and smaller fluctuations during the period of social distancing. Inter-city comparisons show that the PM2.5 concentration changes are positively correlated with the city-wide PM2.5 emission fractions for mobile sources and negatively correlated with the city-wide PM2.5 emission fractions for combustion and industrial process sources. In addition, the meteorological influences favorable for transboundary pollutant transport have weakened during the period under COVID-19 social distancing. Intra-city comparisons show that decreases in the intra-city variability of PM2.5 concentration were larger in coastal cities than in inland cities. Comparisons between the inter- and intra-city variabilities in the PM2.5 concentration changes under social distancing highlight the importance of taking into account intra-city variabilities in addition to inter-city variabilities.


Evaluation of laccase production by Ganoderma lucidum in submerged and solid-state fermentation using different inducers.
Laccases are multicopper oxidases with high potential for industrial applications. Several basidiomycete fungi are natural producers of this enzyme; however, the optimization of production and selection of inducers for increased productivity coupled with low costs is necessary. Lignocellulosic residues are important lignin sources and potential inducers for laccase production. Pinus taeda, a dominant source of wood-based products, has not been investigated for this purpose yet. The aim of this study was to evaluate the production of laccase by the basidiomycete fungus Ganoderma lucidum in the presence of different inducers in submerged and solid-state fermentation. The results of submerged fermentation in presence of 5 μM CuSO 4 , 2 mM ferulic acid, 0.1 g/L P. taeda sawdust, or 0.05 g/L Kraft lignin indicated that although all the tested inducers promoted increase in laccase activity in specific periods of time, the presence of 2 mM ferulic acid resulted in the highest value of laccase activity (49 U/L). Considering the submerged fermentation, experimental design following the Plackett-Burman method showed that the concentrations of ferulic acid and P. taeda sawdust had a significant influence on the laccase activity. The highest value of 785 U/L of laccase activity on submerged fermentation was obtained on the seventh day of cultivation. Finally, solid-state fermentation cultures in P. taeda using ferulic acid or CuSO 4 as inducers resulted in enzymatic activities of 144.62 and 149.89 U/g, respectively, confirming the potential of this approach for laccase production by G. lucidum.


Measurement invariance of the Eating Disorder Examination in black and white children and adolescents.
The Eating Disorder Examination (EDE) was originally developed and validated in primarily white female samples. Since data indicate that eating pathology impacts black youth, elucidating the psychometric appropriateness of the EDE for black youth is crucial. A convenience sample was assembled from seven pediatric obesity studies. The EDE was administered to all youth. Confirmatory factor analyses (CFA) were conducted to examine the original four-factor model fit and two alternative factor structures for black and white youth. With acceptable fit, multiple-group CFAs were conducted. For measurement invariant structures, the interactive effects of race with sex, BMIz, adiposity, and age were explored (all significance levels p < .05). For both black and white youth (N = 820; 41% black; 37% male; 6-18 years; BMIz -3.11 to 3.40), the original four-factor EDE structure and alternative eight-item one-factor structure had mixed fit via CFA. However, a seven-item, three-factor structure reflecting Dietary Restraint, Shape/Weight Overvaluation, and Body Dissatisfaction had good fit and held at the level of strict invariance. Girls reported higher factor scores than boys. BMIz and adiposity were positively associated with each subscale. Age was associated with Dietary Restraint and Body Dissatisfaction. The interactional effects between sex, BMIz, and age with race were not significant; however, the interaction between adiposity and race was significant. At higher adiposity, white youth reported greater pathology than black youth. An abbreviated seven-item, three-factor version of the EDE captures eating pathology equivalently across black and white youth. Full psychometric testing of the modified EDE factor structure in black youth is warranted.


Surgical embolectomy for intermediate-risk acute pulmonary embolism.
Recent series reported excellent results of surgical embolectomy in patients with acute pulmonary embolism with mortality rates of about 5-9% (range 0-13%). However, very low mortality of patients receiving medical treatment for intermediate-risk pulmonary embolism (1.5 and 2.8% at 7 and 30 days, respectively) was recently reported. Thus, we would like to challenge the indication for surgical embolectomy in the subset of intermediate-risk patients.


Heterostructured Ag@MOF-801/MIL-88A(Fe) Nanocomposite as a Biocompatible Photocatalyst for Degradation of Reactive Black 5 under Visible Light.
Heterostructured Ag@MOF-801/MIL-88A(Fe) nanocomposite was synthesized through template effects in metal-organic frameworks (MOFs). MIL-88A(Fe) was fabricated on a MOF-801 template using the internal extended growth method (IEGM) via polyvinylpyrrolidone (PVP) as the structure-director agent to create the MIL-88A(Fe)-on-MOF-801 heterostructure. The MOF-801/MIL-88A(Fe) heterostructure was used as a template for the formation of Ag nanoparticles (NPs) inside it via a double solvents method (DSM) combined with a photoreduction route (PR). To characterize synthesized samples to a high level of detail, PXRD, FT-IR, EDX, N2 adsorption-desorption isotherms, TEM, DRS, PL, EIS, and Mott-Sckottky measurements were used. The resulting Ag@MOF-801/MIL-88A(Fe) nanocomposite demonstrated the highest photocatalytic activity of 91.72% for the degradation of Reactive Black 5, after 30 min under visible light irradiation.


CONSERVATION OF MOLECULAR PREPATTERNS DURING THE EVOLUTION OF CUTICLE MORPHOLOGY IN DROSOPHILA LARVAE.
We are using patterns of cuticle specialization in Drosophila larvae as models to investigate the molecular, genetic, and developmental bases of morphological evolution. Members of the virilis species group differ markedly from one another in the distribution of hairs on the dorsal surface of first instar larvae. In particular, characteristic bands of hairs cover about 20% of each trunk segment in some species but about 70% in others. These major types do not correlate with recently proposed phylogenetic relationships, suggesting that similar phenotypes have arisen independently in different lineages. The patterns of expression of several genes that control or reflect intrasegmental patterning are indistinguishable in species with very different cuticle morphologies. We conclude that, in this case, morphology probably has evolved via altered response to a conserved molecular prepattern.


Therapeutic efficacy of Scutellaria baicalensis Georgi against psoriasis-like lesions via regulating the responses of keratinocyte and macrophage.
Psoriasis is a chronic and recurrent skin problem that affects 3% of the global population. Nowadays, most medicines may not promise a complete cure for patients with psoriasis because of the development of pharmacoresistance and the side effects of drugs due to the microenvironment impact in the context of skin imbalance. Herein, we attempt to explore the pharmaceutical efficacy of Scutellaria baicalensis (S. baicalensis) in modulating the microenvironment created by macrophages and keratinocytes in psoriasis. The results indicated that treatment of S. baicalensis extract significantly reduced the thickness of epidermis and attenuated psoriatic lesions. Moreover, S. baicalensis extract obviously inhibited the activation and infiltration of macrophages by alleviating inflammatory factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and cyclooxygenase-2 (COX-2). The administration of S. baicalensis extract also remarkably abolished oxidative damage upon DNA and proteins, which attributed to the activation of nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1). The network analysis of redox proteomics and cytokine profiles suggested that S. baicalensis administration regulated the specific pathways associated with oxidative stress, inflammation and cytokine signaling cascades to ameliorate the macrophage-targeted responses and subsequently arrest proliferation of keratinocytes. Collectively, our findings highlighted the importance of S. baicalensis application in reprogramming microenvironment to provide an alternative and complementary intervention for long-term psoriatic therapy.


Telaprevir-based therapy for treatment of HIV-1 and hepatitis C virus co-infected patients: An early access programme.
HPC3005 is a multicentre, open-label, telaprevir trial in HCV/HIV coinfected patients with severe fibrosis or compensated cirrhosis. Patients were treated with telaprevir 750 mg every 8 h (1125 mg if on efavirenz) plus pegylated interferon-alpha (PEG-IFN, 180 μg once-weekly) and ribavirin (RBV, 800 mg/day) for 12 weeks, followed by 36 weeks of PEG-IFN/RBV. Mean age was 44 years, 97/118 patients were male and all were Caucasian, 68 had severe fibrosis and 50 had cirrhosis. Seventy-eight had HCV RNA levels ≥800 000 IU/mL, 72 had HCV genotype 1a, baseline HIV RNA was <50 copies/mL in 112 patients. Overall, 114/118 patients continued antiretroviral treatment, 4 were untreated. Seventy-five patients received tenofovir and 74 emtricitabine; in addition 53 received atazanavir/ritonavir, 43 raltegravir, and 24 efavirenz. By intention-to-treat, 78 (66%) patients achieved SVR24. Nineteen discontinued telaprevir, 8 for virological endpoint, 5 for adverse events (2 anaemia, 2 rash, 1 asthenia), 5 for non-compliance and 1 withdrew consent. The most common adverse events were anaemia (36 patients), thrombocytopaenia (33), rash (26), bilirubin increase (17), and neutropenia (16). In this early access programme in coinfected patients with severe fibrosis or cirrhosis, 66% of patients achieved SVR. The most common adverse events were haematological. NCT01500616.


Design of UV-Vis-NIR panchromatic crown-phthalocyanines with controllable aggregation.
Novel magnesium and zinc phthalocyaninates, bearing four lateral electron-rich 15-crown-5-oxanthrene fragments, were synthesized starting from benzo-15-crown-5. Being almost insoluble in common organic solvents, these complexes could be solubilised by interaction with potassium acetate due to the formation of well-defined cofacial supramolecular dimers. A characteristic feature of these dimers is the presence of additional bands in their UV-Vis spectra, which affords the expansion of light absorption region up to ∼750 nm. This new band corresponds to the charge transfer from the peripheral groups to the Pc core, as evidenced by TDDFT calculations. Potassium cations can be reversibly removed from these dimers by [2.2.2]cryptand, resulting in the formation of monodisperse nanoparticles exhibiting absorbances up to 900 nm. This approach can be further used for the fabrication of nanostructured optoelectronic materials based on the synthesized donor-acceptor panchromatic crown-phthalocyanines.


Artificial intelligence, physiological genomics, and precision medicine.
Big data are a major driver in the development of precision medicine. Efficient analysis methods are needed to transform big data into clinically-actionable knowledge. To accomplish this, many researchers are turning toward machine learning (ML), an approach of artificial intelligence (AI) that utilizes modern algorithms to give computers the ability to learn. Much of the effort to advance ML for precision medicine has been focused on the development and implementation of algorithms and the generation of ever larger quantities of genomic sequence data and electronic health records. However, relevance and accuracy of the data are as important as quantity of data in the advancement of ML for precision medicine. For common diseases, physiological genomic readouts in disease-applicable tissues may be an effective surrogate to measure the effect of genetic and environmental factors and their interactions that underlie disease development and progression. Disease-applicable tissue may be difficult to obtain, but there are important exceptions such as kidney needle biopsy specimens. As AI continues to advance, new analytical approaches, including those that go beyond data correlation, need to be developed and ethical issues of AI need to be addressed. Physiological genomic readouts in disease-relevant tissues, combined with advanced AI, can be a powerful approach for precision medicine for common diseases.


[Management of vulvar cancer].
In the treatment of vulvar malignancy surgery, chemotherapy, irradiation therapy and so on can be used. Actually, it was rarely performed only by a single method. For treatment by the stage of cancer progression, the superficial cancer was treated by wide local resection for the patients except old women who were done simple vulvectomy. For the invasive cancer, stage 1 or 2, the pre-operative bleomycin (BLM) was administered to reduce the tumor mass, thereafter, radical vulvectomy with inguinal lymph node resection was performed. If inguinal lymph nodes metastasis was found, area of resection was extended to pelvic lymph nodes. Recently, micro-invasive carcinoma was defined that the foci was below 2 cm and interstitial invasion below 1 mm. In this condition, it was needless to remove the lymph nodes. For the stage of 3 or 4 which was inoperable, chemotherapy (mainly BLM) combined with irradiation therapy was done. In the cases of good general condition, it was chosen by super-radical vulvectomy.


Metabolism of gingival collagen in a rat.
The remodeling of gingival tissue was measured by determining the incorporation of tritiated proline and the disappearance of tritium activity from proline and hydroxyproline for 18 days after administration of label. There was a rapid decrease in the tritium activity from gingiva which was paralleled by a decrease in the total activity of proline. The activity in collagen decreased sharply between the second and the fourth day but thereafter there was no change. The relative amount of activity increased from 24% at day 2 to 82% at 18 days postinjection, and as a result the specific activities of hydroxyproline and proline were similar after 12 days. Thus collagen appeared to be the more stable component in the gingivae than previously reported. However, the rapid loss of label in the first four days suggested that there may be very marked regional variation in the metabolism of collagen and that more than one metabolic pool of collagen was present.


The Ribroast Technique™: An Alternative Method to Stabilize a Resorbable Collagen Membrane for Guided Bone Regeneration.
Stabilization of the graft-membrane complex during guided bone regeneration is a critically important aspect of implant dentistry. Several articles in the dental literature have introduced the utilization of periosteal biting stabilization sutures, rather than fixation screws and pins, to stabilize a bioabsorbable collagen membrane. This article reviews the concept of stabilization using sutures in periodontal regeneration and describes an alternative method, the Ribroast technique™, to stabilize a bioabsorbable membrane, whereby single periosteal biting horizontal mattress sutures are placed along the length of the defect to achieve sufficient stabilization. Two cases are presented that highlight the utility of this technique. Guidelines and limitations for the use of periosteal biting sutures are also discussed along with considerations and protocols that may be useful for improving treatment outcomes.


Talk to Me-Interplay between Mitochondria and Microbiota in Aging.
The existence of mitochondria in eukaryotic host cells as a remnant of former microbial organisms has been widely accepted, as has their fundamental role in several diseases and physiological aging. In recent years, it has become clear that the health, aging, and life span of multicellular hosts are also highly dependent on the still-residing microbiota, e.g., those within the intestinal system. Due to the common evolutionary origin of mitochondria and these microbial commensals, it is intriguing to investigate if there might be a crosstalk based on preserved common properties. In the light of rising knowledge on the gut-brain axis, such crosstalk might severely affect brain homeostasis in aging, as neuronal tissue has a high energy demand and low tolerance for according functional decline. In this review, we summarize what is known about the impact of both mitochondria and the microbiome on the host's aging process and what is known about the aging of both entities. For a long time, bacteria were assumed to be immortal; however, recent evidence indicates their aging and similar observations have been made for mitochondria. Finally, we present pathways by which mitochondria are affected by microbiota and give information about therapeutic anti-aging approaches that are based on current knowledge.


[Y-chromosome haplotypes in Corsica].
We studied the distribution of Y-chromosome specific haplotypes (detected by the TaqI polymorphism of probes p49a,f) on a total of 328 Corsican males native of the regions of Ajaccio, Bastia and Corte. Three haplotypes are differential among regions: haplotype XV (A3 C1 D2 F1 I1), preponderant in the North of the island, haplotype V (A2 C0 D0 F1 I1) in the South, and haplotype XII (A3 C0 D1 F1 I0) in the highlands of the centre. Distribution of haplotypes can be explained by Corsican history and geography.


Pharmacokinetic-pharmacodynamic relationships of cognitive and psychomotor effects of intravenous buprenorphine infusion in human volunteers.
The main objective of the present study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of the effects of buprenorphine on cognitive functioning in healthy volunteers. Twenty-three male volunteers received 0.6 mg buprenorphine as an intravenous infusion over 150 min. The cognitive and psychomotor performance was evaluated before and at various times after drug administration by a test battery consisting of trail-making test for visual information processing, finger-tapping test for psychomotor speed, and continuous reaction time for attention. Non-linear mixed effect modelling was used in the analysis of the PK/PD relationships. Buprenorphine caused significant deficits in cognitive and psychomotor functioning. The time course of cognitive and psychomotor impairment was found to have a slow distribution to the biophase from plasma with PK/PD models involving an effect compartment providing the best descriptions of the time course of the data. The values for half-life of biophase equilibration were consistent between the neuropsychological tests in the range of 66.6-84.9 min. The time to onset and duration of the cognitive and psychomotor impairment of buprenorphine was determined by a slow distribution to the biophase.