Heat shock protein 65 induced by gammadelta T cells prevents apoptosis of macrophages and contributes to host defense in mice infected with Toxoplasma gondii.
We previously reported that gammadelta T cells mediate the expression of endogenous heat shock protein 65 (HSP65) in macrophages of mice with acquired resistance against infection with Toxoplasma gondii. We show here that HSP65 contributes to protective immunity by preventing apoptosis of infected macrophages. Macrophages of BALB/c mice, which readily acquired resistance to T. gondii infection with the low virulence Beverley strain, strongly expressed HSP65, and only a few of these macrophages underwent apoptosis. On the other hand, the BALB/c mice were susceptible to the infection with the high virulence RH strain of T. gondii; their macrophages did not express HSP65 and did undergo apoptosis. Mice depleted of gammadelta T cells using a mAb specific for TCR-gammadelta became highly susceptible to infection even with the Beverley strain. In these mice, HSP65 expression was markedly suppressed, and their infected macrophages died via apoptosis. Apoptosis was induced in cultured macrophages or macrophage cell lines after infection in vitro with the RH strain, whereas apoptosis was prevented when HSP65 was induced in these cells, before infection, by activation with IFN-gamma and TNF-alpha. However, apoptosis associated with infection by T. gondii RH strain was not prevented when HSP65 synthesis was inhibited by introducing an antisense oligonucleotide for this protein into the cells before activation with IFN-gamma plus TNF-alpha. Thus, HSP65 appears to contribute to immunity by preventing the apoptosis of infected macrophages, and the high virulence Toxoplasma appears to have mechanisms that allow these organisms to evade the host defense system by interfering with HSP65 expression.


Chemical Features and Machine Learning Assisted Predictions of Protein-Ligand Short Hydrogen Bonds.
There are continuous efforts to elucidate the structure and biological functions of short hydrogen bonds (SHBs), whose donor and acceptor heteroatoms reside more than 0.3 A closer than the sum of their van der Waals radii. In this work, we evaluate 1070 atomic-resolution protein structures and characterize the common chemical features of SHBs formed between the side chains of amino acids and small molecule ligands. We then develop a machine learning assisted prediction of protein-ligand SHBs (MAPSHB-Ligand) model and reveal that the types of amino acids and ligand functional groups as well as the sequence of neighboring residues are essential factors that determine the class of protein-ligand hydrogen bonds. The MAPSHB-Ligand model and its implementation on our web server enable the effective identification of protein-ligand SHBs in proteins, which will facilitate the design of biomolecules and ligands that exploit these close contacts for enhanced functions.


Clostridium perfringens alpha toxin affects electrophysiological properties of isolated jejunal mucosa of laying hens.
Bacteria that colonize the intestinal tract can invade epithelial cells or produce toxins that cause diarrhoeal diseases. Proliferation of Clostridium perfringens and production of alpha-toxin, a phospholipase C, is the major factor for necrotic enteritis in poultry. However, little is known about the functional importance of luminal alpha-toxin during intestinal infection. The purpose of this study was to investigate the effects of purified alpha toxin of Clostridium perfringens on the electrophysiology of the laying hen's stripped jejunum in Ussing chambers. The effects were investigated in Experiment 1 after toxin addition to the mucosal and serosal side of the tissue, and a second experiment was performed to study the effect of the toxin on sodium-dependent glucose transport. Mucosal exposure of jejunal tissue sheets to 100 units of alpha toxin/L did not elicit electrophysiologic changes. The addition of purified alpha toxin to the serosal side induced a biphasic increase in short-circuit current (ISC) after 15 and 100 min. The magnitude of the increase of ISC of both peaks was similar, but the second phase response lasted longer. The tissue conductivity tended (P = 0.07) to be lower after 2 h of toxin addition compared with basal value when no toxin was added. In the second experiment, adding D-glucose on the mucosal side of the jejunum increased (P < 0.05) the ISC from a baseline value of 42 +/- 28 microA/cm2 to a maximal value of 103 +/- 27 microA/cm2. Preincubation with alpha-toxin almost fully inhibited this stimulation of ISC by D-glucose. The conductance of the tissues was not affected by the toxin addition. These findings indicate that alpha toxin not only causes electrogenic secretion of anions, probably due to the stimulation of chloride secretion, but also diminishes electrogenic Na+/glucose cotransport from the mucosal to serosal side in the small intestine of poultry.


Simulation-based training in Leprosy: development and validation of a scenario for community health workers.
To build and validate a clinical simulation scenario designed to instruct community health workers (CHWs) in active leprosy case detection. Methodological study involving the development of a simulated clinical scenario and content validation by experts. The Content Validity Index (CVI) was used to determine the level of agreement among the judging commitee, and a descriptive analysis of their recommendations was performed. A simulated scenario with a simulated participant was developed - a simulation characterized by low complexity, moderate physical/environmental fidelity, moderate to high psychological fidelity, and high conceptual fidelity, lasting 50 minutes and capable of training up to 10 CHWs simultaneously. The scenario was validated by 14 experts, with a CVI exceeding 80% for all components. The validated clinical simulation possesses attributes that make it highly reproducible in various national health contexts, thereby contributing to the global "Towards Zero Leprosy" strategy.


One recognition sequence, seven restriction enzymes, five reaction mechanisms.
The diversity of reaction mechanisms employed by Type II restriction enzymes was investigated by analysing the reactions of seven endonucleases at the same DNA sequence. NarI, KasI, Mly113I, SfoI, EgeI, EheI and BbeI cleave DNA at several different positions in the sequence 5'-GGCGCC-3'. Their reactions on plasmids with one or two copies of this sequence revealed five distinct mechanisms. These differ in terms of the number of sites the enzyme binds, and the number of phosphodiester bonds cleaved per turnover. NarI binds two sites, but cleaves only one bond per DNA-binding event. KasI also cuts only one bond per turnover but acts at individual sites, preferring intact to nicked sites. Mly113I cuts both strands of its recognition sites, but shows full activity only when bound to two sites, which are then cleaved concertedly. SfoI, EgeI and EheI cut both strands at individual sites, in the manner historically considered as normal for Type II enzymes. Finally, BbeI displays an absolute requirement for two sites in close physical proximity, which are cleaved concertedly. The range of reaction mechanisms for restriction enzymes is thus larger than commonly imagined, as is the number of enzymes needing two recognition sites.


Immunodeficient states and associated rheumatic manifestations.
The molecular mechanisms of the primary immunodeficiencies have been further explored and provide insights into the regulation of the immune response and its role in autoimmune disease, infection, and malignancy. The critical role of CD40-CD40 ligand-mediated effects in T cell-dependent B cell activation, shown through the study of patients with common variable immunodeficiency and hyper IgM syndrome, suggests a potential narrow target for immunomodulatory therapy. A mouse model for chronic granulomatous disease has been developed and promises to be a source of future information. Optimal cost-effective therapy for primary immunodeficiencies continues to be defined, with the results of a large series of patients treated with subcutaneous immunoglobulin infusions reported. Further experience with polyethylene glycol adenosine deaminase and interleukin-2 conjugates is discussed.


Inauguration of the cameroonian society of human genetics.
The conjunction of "hard genetics" research centers, with well established biomedical and bioethics research groups, and the exceptional possibility to hold the 6th annual meeting of the African Society of Human Genetics (AfSHG, 13th-15th March 2009) was an excellent opportunity to get together in synergy the entire Cameroonian "DNA/RNA scientists" . This laid to the foundation of the Cameroonian Society of Human Genetics (CSHG) that was privilege to hold its inaugural meeting in conjunction to the 6th annual meeting of the AfSHG. The theme was "Human Origin, Genetic Diversity and Health". The AfSHG and CSHG invited leading African and international scientists in genomics and population genetics to review recent data and provide an understanding of the state-of-knowledge of Human Origin and Genetic Diversity. Overall one opening ceremony eight session, five keynote and guest speakers, 18 invited oral communications, 13 free oral communications, 43 posters and two social events could summarize the meeting. This year's conference was graced by the presence of one Nobel Prize winner Dr Richard Roberts (Physiology and Medicine 1993). The meeting registered up to ten contributions of Cameroonian scientists from the Diaspora (currently in USA, Belgium, Gambia, Sudan and Zimbabwe). Such Diaspora participation is an opportunity to generate collaborations with home country scientists and ultimately turn the "brain drain" to "brain circulation" that could reduce the impact of the migration of health professional from Africa. Interestingly, the personal implication of the Cameroonian Ministry of Public Heath who opened the meeting in the presence of the Secretary General of the Ministry of Higher Education and a representative of the Ministry of Scientific Research and Innovation was a wonderful opportunity for advocacy of genetic issues at the decision-makers level. Beyond our expectation, a major promise of the Cameroonian government was the creation of the National Human Genome Institute. If this goal comes true, this will be a critical step to bring more genetics for the purpose of Public Health to the Cameroonian people. The sub-Saharan African Region needs significant capacity building in the broad area of basic research in general and Genetics (especially Human Genetics) in particular. In that respect, the existence and current activities of the AfSHG and its impact at the National levels in Africa, is a major development for the continent and an initiative that needs further encouragement from the international community.


Enhancing Upland cotton for drought resilience, productivity, and fiber quality: comparative evaluation and genetic dissection.
To provision the world sustainably, modern society must increase overall crop production, while conserving and preserving natural resources. Producing more with diminishing water resources is an especially daunting endeavor. Toward the goal of genetically improving drought resilience of cultivated Upland cotton (Gossypium hirsutum L.), this study addresses the genetics of differential yield components referred to as productivity and fiber quality traits under regular-water versus low-water (LW) field conditions. We used ten traits to assess water stress deficit, which included six productivity and four fiber quality traits on two recombinant inbred line (RIL) populations from reciprocally crossed cultivars, Phytogen 72 and Stoneville 474. To facilitate genetic inferences, we genotyped RILs with the CottonSNP63K array, assembled high-density linkage maps of over 7000 SNPs and then analyzed quantitative trait variations. Analysis of variance revealed significant differences for all traits (p < 0.05) in these RIL populations. Although the LW irrigation regime significantly reduced all traits, except lint percent, the RILs exhibited a broad phenotypic spectrum of heritable differences across the water regimes. Transgressive segregation occurred among the RILs, suggesting the possibility of genetic gain through phenotypic selection for drought resilience and perhaps through marker-based selection. Analyses revealed more than 150 quantitative trait loci (QTLs) associated with productivity and fiber quality traits (p < 0.005) on different genomic regions of the cotton genome. The multiple-QTL models analysis with LOD > 3.0 detected 21 QTLs associated with productivity and 22 QTLs associated with fiber quality. For fiber traits, strong clustering and QTL associations occurred in c08 and its homolog c24 as well as c10, c14, and c21. Using contemporary genome sequence assemblies and bioinformatically related information, the identification of genomic regions associated with responses to plant stress/drought elevates the possibility of using marker-assisted and omics-based selection to enhance breeding for drought resilient cultivars and identifying candidate genes and networks. RILs with different responses to drought indicated that it is possible to maintain high fiber quality under LW conditions or reduce the of LW impact on quality. The heritable variation among elite bi-parental RILs for productivity and quality under field drought conditions, and their association of QTLs, and thus specific genomic regions, indicate opportunities for breeding-based gains in water resource conservation, i.e., enhancing cotton's agricultural sustainability.


Intensive Hemodialysis Preserved Cardiac injury.
Cardiac injury triggers cellular responses involving both cardiomyocytes and nonmuscle cells to process cardiac structural remodeling. End-stage renal disease (ESRD), despite conventional dialysis, is associated with adverse cardiac remodeling and increased cardiovascular events. Intensification of hemodialysis with nocturnal home hemodialysis (NHD; five sessions per week; 6-8 hours per treatment) was associated with regression of left ventricular hypertrophy and downregulation of genes in apoptosis and fibrosis. In this pilot study, we hypothesize that NHD achieves its cardiac effects in part through attenuation of innate immune activation resulting in amelioration of cardiomyocytes apoptosis and fibrosis. Eight patients (4M:4F; age, 59 ± 9 years) with ESRD were studied. Half of the cohort was converted to NHD, whereas the rest of the patients were maintained on conventional hemodialysis (CHD). At baseline, CHD was associated with an increase in cardiomyocyte apoptosis detected by flow cytometry using Annexin V (mean fluorescence index in CHD and in normal control is 1.00 ± 0.05 vs. 0.66 ± 0.01, p < 0.05). After conversion to NHD, cardiomyocyte apoptosis was reduced compared with baseline CHD situation (p < 0.05) and approached that of normal control (0.59 ± 0.09 vs. 0.66 ± 0.01, p > 0.05). The CHD serum was associated with a coordinated augmentation innate immunity pathway, significantly increasing myeloid differentiation factor-88 and interleukin-1 receptor-associated kinase-4; NHD was able to reduce their levels. Heat shock protein 60 was augmented during CHD condition and fell after NHD. In addition, CHD increased fibroblast proliferation and myofibroblast transformation. Uremia is associated with activation of common innate immune signaling pathways leading to fibrosis and apoptosis. Amelioration of uremic clearance by NHD may attenuate this pathological signaling cascade.


Evaluation of a hospital-based injury surveillance system for monitoring road traffic deaths in Phuket, Thailand.
Objectives: The objective of this study was to evaluate and injury surveillance (IS) system's ability to monitor road traffic deaths and the coverage of road traffic injury and death surveillance in Phuket, Thailand. Methods: U.S. Centers for Disease Control and Prevention guidelines on surveillance system evaluation were used to qualitatively and quantitatively evaluate IS. Interviews with key stakeholders focused on IS's usefulness, simplicity, flexibility, acceptability, and stability. Active case finding of 2014 road traffic deaths in all paper and electronic hospital record systems was used to assess system sensitivity, positive predictive value, and data quality. Electronic data matching software was used to determine the implications of combining IS data with other provincial-level data sources (e.g., death certificates, electronic vehicle insurance claim system). Results: Evaluation results indicated that IS was useful, flexible, acceptable, and stable, with a high positive predictive value (99%). Simplicity was limited due to the burden of collecting data on all injuries and use of paper-based data collection forms. Sensitivity was low, with IS only identifying 55% of hospital road traffic death cases identified during active case finding; however, IS cases were representative of cases identified. Data accuracy and completeness varied across data fields. Combining IS with active case finding, death certificates, and the electronic vehicle insurance claim system more than doubled the number of road traffic death cases identified in Phuket. Conclusion: An efficient and comprehensive road traffic injury and death surveillance system is critical for monitoring Phuket's road traffic burden. The hospital-based IS system is a useful system for monitoring road traffic deaths and assessing risk behaviors. However, the complexity of data collection and limited coverage hinders the ability of IS to fully represent road traffic deaths in Phuket Province. Combining data sources could improve coverage and should be considered.


Hepatoencephalopathy syndrome due to Cassia occidentalis (Leguminosae, Caesalpinioideae) seed ingestion in horses.
Cassia occidentalis is a bush from the Leguminosae family, subfamily Caesalpinoideae, and is a toxic plant of veterinary interest due to the occasional contamination of animal rations. This report describes the clinical and histopathological findings of an outbreak of C. occidentalis poisoning in horses. Twenty mares were poisoned after consuming ground corn contaminated with 8% of C. occidentalis seeds. Of the 20 animals affected, 12 died: 8 mares were found dead, 2 died 6 h after the onset of clinical signs compatible with hepatic encephalopathy and the 2 other animals were subjected to euthanasia 12 h after the onset of the clinical signs. The remaining 8 mares presented with mild depression and decreased appetite, but improved with treatment and no clinical sequelae were observed. In 6 animals that underwent a necropsy, an enhanced hepatic lobular pattern was noted and within the large intestine, a large number of seeds were consistently observed. Hepatocellular pericentrolobular necrosis and cerebral oedema were the main histological findings. In one mare, there was mild multifocal semimembranosus rhabdomyocytic necrosis and haemorrhage. Seeds collected from intestinal contents and sifted from the culpable feedstuff were planted. Examination of the leaves, flowers, fruits and seeds of the resultant plants identified C. occidentalis. Horses poisoned by C. occidentalis seeds demonstrate clinical signs associated with hepatoencephalopathy and frequently die suddenly. Lesions primarily involve the liver and secondarily, the central nervous system. Cassia occidentalis poisoning should be considered a differential diagnosis in horses with hepatoencephalopathy and special caution should be taken with horse rations to avoid contamination with seeds of this toxic plant.


The role of mismatch repair in the prevention of base pair mutations in Saccharomyces cerevisiae.
In most organisms, the mismatch repair (MMR) system plays an important role in substantially lowering mutation rates and blocking recombination between nonidentical sequences. In Saccharomyces cerevisiae, the products of three genes homologous to Escherichia coli mutS-MSH2, MSH3, and MSH6-function in MMR by recognizing mispaired bases. To determine the effect of MMR on single-base pair mismatches, we have measured reversion rates of specific point mutations in the CYC1 gene in both wild-type and MMR-deficient strains. The reversion rates of all of the point mutations are similar in wild-type cells. However, we find that in the absence of MSH2 or MSH6, but not MSH3, reversion rates of some mutations are increased by up to 60,000-fold, whereas reversion rates of other mutations are essentially unchanged. When cells are grown anaerobically, the reversion rates in MMR-deficient strains are decreased by as much as a factor of 60. We suggest that the high reversion rates observed in these MMR-deficient strains are caused by misincorporations opposite oxidatively damaged bases and that MMR normally prevents these mutations. We further suggest that recognition of mispairs opposite damaged bases may be a more important role for MMR in yeast than correction of errors opposite normal bases.


Dibenzoylmethane activates Nrf2-dependent detoxification pathway and inhibits benzo(a)pyrene induced DNA adducts in lungs.
Cigarette smoke derived carcinogens have been identified as the main agents implicated in lung carcinogenesis. Epidemiological as well as animal studies have indicated that certain phytochemicals can block the carcinogenic process by enhancing the detoxification of environmental and or dietary carcinogens. Dibenzoylmethane (DBM), a minor constituent of licorice, is a beta-ketone analog of curcumin, a promising chemopreventive agent for colon, breast and skin cancer. The present study was designed to examine the chemopreventive efficacy of DBM in lungs, its global molecular targets and the mechanism of its action. Feeding DBM to A/J mice significantly inhibited benzo[a]pyrene induced DNA adducts in lungs. Further analysis of its global molecular targets in lungs by oligonucleotide microarray revealed expression of several cytoprotective genes including phase II enzymes that are regulated by Nrf2, a basic leucine zipper transcription factor. To decipher if DBM mediates its function via Nrf2 activation, Nrf2 dependent reporter assays were performed. DBM elicited a dose-dependent increase in antioxidant response element (ARE)-driven luciferase reporter activity which correlated with an increase in mRNA expression of NQO1, GSTA2, and GCLC in mouse hepatoma cells, which are well established targets of Nrf2. Conversely, DBM stimulated ARE reporter activity was attenuated by a dominant-negative mutant of Nrf2. Electrophoretic mobility shift assay confirmed that DBM greatly increased the DNA binding activity of Nrf2. In conclusion, DBM mediates the induction of phase II enzymes by Nrf2 activation and inhibits benzo[a]pyrene induced DNA adducts by enhancing its detoxification in lungs.


CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment.
Glioblastoma (GBM) patients suffer from a dismal prognosis, with standard of care therapy inevitably leading to therapy-resistant recurrent tumors. The presence of cancer stem cells (CSCs) drives the extensive heterogeneity seen in GBM, prompting the need for novel therapies specifically targeting this subset of tumor-driving cells. Here, we identify CD70 as a potential therapeutic target for recurrent GBM CSCs. In the current study, we identified the relevance and functional influence of CD70 on primary and recurrent GBM cells, and further define its function using established stem cell assays. We use CD70 knockdown studies, subsequent RNAseq pathway analysis, and in vivo xenotransplantation to validate CD70's role in GBM. Next, we developed and tested an anti-CD70 chimeric antigen receptor (CAR)-T therapy, which we validated in vitro and in vivo using our established preclinical model of human GBM. Lastly, we explored the importance of CD70 in the tumor immune microenvironment (TIME) by assessing the presence of its receptor, CD27, in immune infiltrates derived from freshly resected GBM tumor samples. CD70 expression is elevated in recurrent GBM and CD70 knockdown reduces tumorigenicity in vitro and in vivo. CD70 CAR-T therapy significantly improves prognosis in vivo. We also found CD27 to be present on the cell surface of multiple relevant GBM TIME cell populations, notably putative M1 macrophages and CD4 T cells. CD70 plays a key role in recurrent GBM cell aggressiveness and maintenance. Immunotherapeutic targeting of CD70 significantly improves survival in animal models and the CD70/CD27 axis may be a viable polytherapeutic avenue to co-target both GBM and its TIME.


The structural effect of the E148Q MEFV mutation on the pyrin protein: a study using a quantum chemistry model.
Familial Mediterranean fever (FMF) is a recessively inherited disease with a variety of clinical presentations. The disease is associated with mutations in the FMF gene (MEFV), which encodes for the pyrin protein. The role of the E148Q pyrin mutation in the FMF phenotype remains inconclusive, and some authors even view it as a disease-insignificant polymorphism. The calculated change imposed by this mutation on pyrin structure may help to understand the role of this mutation. To calculate the relative electrochemical effect of the E148Q mutation on the structure of pyrin protein. The electronic properties of the wild-type pyrin molecule and its common mutated forms were computed for the full-length molecule and its segments, encoded by exons 2 and 10, using the HyperChem 7.5 program with one of the molecular mechanical methods (MM+). The change in the structure of the molecule, expressed as a change in energy gain, conferred by the mutations was determined. The E148Q mutation caused deviation from the wildtype pyrin segment encoded by exon 2 by 1.15% and from the whole pyrin molecule by 0.75%, which was comparable to the R202Q mutation and less than the M694V mutation which caused a deviation from the wild-type structure of the whole pyrin molecule by 1.5%. A quantum chemistry-based model suggests that the structural effect of the E148Q mutation is indeed low but not zero.


Pan-Cancer Analysis of Voltage-Dependent Anion Channel (VDAC1) as a Cancer Therapeutic Target or Diagnostic Biomarker.
The voltage-dependent anion channel 1 (VDAC1), a pore protein located in the outer mitochondrial membrane, has been confirmed to be related to cancer in cell or animal evidence. However, there is no available pan-cancer analysis of VDAC1. Herein, we investigated the potential roles of VDAC1 in tumorigenesis and progression based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets. The expression of VDAC1 increased in most cancers, and the upregulation of VDAC1 distinctly correlated with the poor prognosis in patients, including breast invasive carcinoma, cervical squamous cell carcinoma, pancreatic adenocarcinoma, lung adenocarcinoma, and skin cutaneous melanoma. We also found VDAC1 S104 phosphorylation raised in various cancers, such as breast cancer, colon cancer, and lung adenocarcinoma. Moreover, the expression of VDAC1 was related to the estimated infiltration value of cancer-associated fibroblasts in bladder urothelial carcinoma, colon adenocarcinoma, kidney renal papillary cell carcinoma, and testicular germ cell tumors. At last, we showed that VDAC1-related oxidative phosphorylation and metabolic regulation may partially explain its association with tumorigenesis and progression. Taken together, this pan-cancer analysis provides relatively comprehensive information on the potential value of VDAC1 as a prognostic biomarker and therapeutic target.


Non-cell autonomous effects of targeting inducible PGE2 synthesis during inflammation-associated colon carcinogenesis.
Microsomal PGE2 synthase-1 (mPGES-1), the terminal enzyme in the formation of inducible PGE2, represents a potential target for cancer chemoprevention. We have previously shown that genetic abrogation of mPGES-1 significantly suppresses tumorigenesis in two preclinical models of intestinal cancer. In this study, we examined the role of mPGES-1 during colon tumorigenesis in the presence of dextran sulfate sodium (DSS)-induced inflammatory microenvironment. Using Apc (Δ14/+) in which the mPGES-1 gene is either wild-type (D14:WT) or deleted (D14:KO), we report that mPGES-1 deficiency enhances sensitivity to acute mucosal injury. As a result of the increased epithelial damage, protection against adenoma formation is unexpectedly compromised in the D14:KO mice. Examining the DSS-induced acute injury, cryptal structures are formed within inflamed areas of colonic mucosa of both genotypes that display the hallmarks of early neoplasia. When acute epithelial injury is balanced by titration of DSS exposures, however, these small cryptal lesions progress rapidly to adenomas in the D14:WT mice. Given that mPGES-1 is highly expressed within the intestinal stroma under the inflammatory conditions of DSS-induced ulceration, we propose a complex and dual role for inducible PGE2 synthesis within the colonic mucosa. Our data suggest that inducible PGE2 is critical for the maintenance of an intact colonic epithelial barrier, while promoting epithelial regeneration. This function is exploited during neoplastic transformation in Apc (Δ14/+) mice as PGE2 contributes to the growth and expansion of the early initiated cryptal structures. Taken together, inducible PGE2 plays a complex role in inflammation-associated cancers that requires further analysis. Inducible PGE2 production by mPGES-1 is critical for the colonic mucosal homeostasis. This function is exploited in the presence of the neoplastic transformation in Apc (Δ14/+) mice as PGE2 contributes to the growth and expansion of the early cryptal structures.


Functional organization of the Aspergillus nidulans trpC promoter.
We investigated the functional organization of the Aspergillus nidulans trpC promoter by the sequential removal of sequences upstream of the major trpC mRNA cap site (+1). DNA fragments containing promoter mutations were fused to the Escherichia coli lacZ gene, and a novel method was used to select for integration of the fusion gene at the Aspergillus argB locus. beta-Galactosidase assays and S1 nuclease protection experiments demonstrated that the promoter mutations affected gene expression in three ways: (i) 5' deletions up to -82 resulted in variable increases in beta-galactosidase activity, depending on the growth conditions; (ii) a deletion from -67 to -11 did not alter the level of beta-galactosidase activity, but did give rise to mRNAs with aberrant 5' ends; and (iii) a 5' deletion with an endpoint at -11 and an internal deletion from -142 to -11 abolished gene expression. These results indicate that sequences upstream of -82 reduce transcription of the trpC gene and that distinct DNA sequence elements are required for expression versus correct initiation of transcription of the trpC gene. The sequences essential for trpC expression do not include the common eucaryotic promoter elements CCAAT and TATAAA. To our knowledge, this is the first functional analysis of a promoter from a fungus other than Saccharomyces cerevisiae.


Periodontal cell implantation contributes to the regeneration of the periodontium in an indirect way.
Periodontitis is the most common human infectious disease. Regeneration of bone and soft tissue defects after periodontitis remains challenging, although the transplantation of periodontal ligament (PDL) cells seems a liable strategy. However, little is known about the function of PDL cells after transplantation. In the current study, a combination of in vitro coculture systems and in vivo immunohistochemistry (IHC) was used to investigate the role of PDL cells in the regenerative process. First, a coculture method was used, in which mesenchymal cells (representing the host tissue) were brought into direct contact with PDL cells (representing the transplanted cell population). It was found that PDL cells significantly increased mineralized matrix formation and osteocalcin expression, whereas control cells did not. Similar results were obtained when a noncontact coculture system was applied separating PDL and mesenchymal cells. In an in vivo rat model, regeneration of alveolar bone and ligament was seen after PDL cell transplantation. Implanted PDL cells were found clustered along the newly formed tissues. IHC showed enhanced osteopontin expression and gap junction staining in areas neighboring implanted PDL cells. In conclusion, PDL cells enhance periodontal regeneration through a trophic factor stimulating the osteogenic activity of the surrounding host cells.


[Role of heparin in the formation of food lipemia].
Influence of endogenic and exogenic heparin in vivo on the basic forms of serum lipids content: cholesterol ethers, triacylglycerols, free fatty acids; as well as that glycosaminoglycan effect in vivo and in vitro on total lipoproteine lipase (LPL) activity and lecithin-cholesterol acyltransferase (LCAT) activity of human blood serum were investigated on food lipidemia model. The decrease of intercell reserve heparin content and increase of the background and post-heparin levels of blood serum LPL activity were indicated after two hours food load. The role of two factors, endogenic heparin being one of them, in the increase of postprandial LPL activity of blood serum were discussed. At the same time, some inhibition of blood serum LCAT activity two hours after food reception (evidently, as a result of endogenic heparin action) and to a considerable extent inhibition of cholesterol etherification under the action of exogenic heparin in vivo were ascertain. Heparin in vitro (50 U/ml of blood serum) did not influence LCAT and total LPL activities. It was summarised that endogenic heparin is a factor, taking part in lipolysis processes regulation.


[Gamasid mites (Gamasina) of rodents in the natural biotopes of Tchui Valley].
The recent fauna of gamasid mites parasitising rodents in the natural biotopes of Tchui Valley (Kyrgyzstan) in investigated. 32 species of Gamasina are revealed, of which 9 are recorded in the region for the first time. A checklist of the gamasid mites is given.


Laser Doppler perfusion monitoring and imaging: novel approaches.
Laser Doppler flowmetry (LDF) is a non invasive method enabling the monitoring of microvascular blood flow, a very important marker of tissue health. This article gives an overview on the concept of LDF for microvascular perfusion monitoring and imaging. It first describes the theoretical background of the technique. Then, the benefits of LDF signal processing are shown through clinical examples: use of time-frequency representations and wavelets. Afterwards, the paper introduces novel approaches of velocity components. For that purpose, a work providing the determination of the velocities relative contribution in physiologically relevant units (mm/s) is presented. Imaging perfusion is also reviewed through methods based on laser speckle. The most prominent disadvantage of the latter devices being the time needed to produce a perfusion image, solutions are proposed in the last part of the paper.


Falls and fall injuries among adults with arthritis--United States, 2012.
Falls are the leading cause of injury-related morbidity and mortality among older adults, with more than one in three older adults falling each year, resulting in direct medical costs of nearly $30 billion. Some of the major consequences of falls among older adults are hip fractures, brain injuries, decline in functional abilities, and reductions in social and physical activities. Although the burden of falls among older adults is well-documented, research suggests that falls and fall injuries are also common among middle-aged adults. One risk factor for falling is poor neuromuscular function (i.e., gait speed and balance), which is common among persons with arthritis. In the United States, the prevalence of arthritis is highest among middle-aged adults (aged 45-64 years) (30.2%) and older adults (aged ≥65 years) (49.7%), and these populations account for 52% of U.S. adults. Moreover, arthritis is the most common cause of disability. To examine the prevalence of falls among middle-aged and older adults with arthritis in different states/territories, CDC analyzed data from the 2012 Behavioral Risk Factor Surveillance System (BRFSS) to assess the state-specific prevalence of having fallen and having experienced a fall injury in the past 12 months among adults aged ≥45 years with and without doctor-diagnosed arthritis. This report summarizes the results of that analysis, which found that for all 50 states and the District of Columbia (DC), the prevalence of any fall (one or more), two or more falls, and fall injuries in the past 12 months was significantly higher among adults with arthritis compared with those without arthritis. The prevalence of falls and fall injuries is high among adults with arthritis but can be addressed through greater dissemination of arthritis management and fall prevention programs in clinical and community practice.


Neuromodulation in treatment of refractory headaches.
The field of neuromodulation is emerging as a promising and alternative therapeutical option for many drug-resistant clinical conditions, including painful syndromes such as refractory chronic cluster headache (CCH) and trigeminal neuralgia. We here report a series of patients who have undergone Deep Brain Stimulation (DBS) of Posterior Hypothalamus for chronic cluster headache, trigeminal neuralgia and atypical facial pain, matching their corresponding clinical results and also suggesting a role for Great Occipital Nerve Stimulation (which is a much less invasive procedure) in the treatment of CCH. According to us, the refinement of surgical techniques and of metabolic and functional brain neuroradiological investigations will lead to a refinement of the therapeutical strategies in such patients.


[Influence of income on food expenditures away from home among Brazilian families, 2002-2003].
This study describes and evaluates the influence of income on the percentage of food expenditures away from home for Brazilian families. Food acquisition data from the National Household Budget Survey conducted from 2002 to 2003 (POF 2002/2003) by the Brazilian Institute of Geography and Statistics (IBGE) or National Census Bureau was used in the analysis. Information on food-and-drink expenditures away from home was analyzed. The influence of income on the share of food purchased away from home in the household budget, adjusted for socio-demographic variables, was analyzed through elasticity coefficients estimated in multiple linear regression. Food purchased away from home accounted for 21% of total food expenditures by Brazilian households. A 10% increase in income increased the share of food purchased away from home by 3%. Income elasticity was high, especially for the lowest income families. The results demonstrate an important influence of income on food expenditures away from home, and higher income is associated with a greater share of food purchased away from home.


An integrative literature review of interventions to reduce violence against emergency department nurses.
To critique the evidence that underpins interventions intended to minimise workplace violence directed against emergency department nurses, to inform researchers and policy makers regarding the design, development, implementation and evaluation of emergency nursing anti-violence and counter-violence interventions. Workplace violence perpetrated against emergency department nurses is at least continuing and at worst increasing. Occupational violence has detrimental effects on job satisfaction, retention and recruitment, and the quality and cost of patient care. An integrated literature review. Searches of the Cochrane Library, CINAHL, MEDLINE and the Joanna Briggs Institute between 1986-May 2007. Included articles were appraised and then synthesised into a narrative summary. Ten primary research studies were included. Interventions were classified as environmental, practices and policies, or skills. While each study has useful information regarding the implementation of interventions, there is no strong evidence for their efficacy. The weight of effort is still directed towards defining the phenomenon rather than addressing solutions. Studies that assessed the efficacy of a single intervention failed to take account of context; and participatory context-driven studies failed to provide generalisable evidence. Concerted multi-site and multi-disciplinary, action-oriented research studies are urgently needed to provide an evidence base for the prevention and mitigation of violence perpetrated against emergency department nurses. The investigation of interventions rather than repeatedly redefining the problem and directing resources into debating semantics or differentiating 'degrees' of violence and aggression is recommended. This review unambiguously identifies the gap in research-based interventions.


Longitudinal in vivo monitoring of rodent glioma models through thinned skull using laser speckle contrast imaging.
Laser speckle contrast imaging (LSCI) is a contrast agent free imaging technique suited for longitudinal assessment of vascular remodeling that accompanies brain tumor growth. We report the use of LSCI to monitor vascular changes in a rodent glioma model. Ten rats are inoculated with 9L gliosarcoma cells, and the angiogenic response is monitored five times over two weeks through a thinned skull imaging window. We are able to visualize neovascularization and measure the number of vessels per unit area to assess quantitatively the microvessel density (MVD). Spatial spread of MVD reveals regions of high MVD that may correspond to tumor location. Whole-field average MVD values increase with time in the tumor group but are fairly stable in the control groups. Statistical analysis shows significant differences in MVD values between the tumor group and both saline-receiving and unperturbed control groups over the two-week period (p<0.05). In conclusion, LSCI is suitable for investigation of tumor angiogenesis in rodent models. In addition, the statistical difference (p<0.02) between MVD values of the tumor (24.40 ± 1.41) and control groups (15.40 ± 1.60) on the 14th day after inoculation suggests a potential use of LSCI in the clinic in distinguishing tumor environments from normal vasculature.


Electronic Prescribing and Medication Management at a Residential Aged Care Facility: Uptake by General Practitioners and Qualitative Evaluation of the Benefits and Barriers.
A cloud-based mobile electronic prescribing and medication management system (ePMMS), in which prescribers' orders directly populate residential aged care facility (RACF) medication administration records (MARs) and are communicated electronically to the RACF's pharmacy, may create efficiencies and improve patient safety when compared to the paper-based and hybrid paper-electronic medication management systems used in most Australian RACFs. Little is known about general-practitioners' (GPs'), nurses' and pharmacists' acceptance of, or experiences with, ePMMS. To explore the uptake of an ePMMS by GPs, and the experiences and perceptions of GPs, nurses and pharmacists, at a 90-bed RACF that tested a beta-version ePMMS. Retrospective audit to determine the proportion of medicines ordered by GPs via the ePMMS over a three-month period. Focus groups conducted three-to-four months after implementation: one with GPs (n=5), one with nurses (n=12); in-depth interview/survey of pharmacists (n=2). Qualitative data were analysed thematically. Three of seven GPs used the ePMMS to order medicines; 53/205(25.9%) medicines were ordered via the ePMMS by GPs. Two broad themes were identified: benefits of the ePMMS, and barriers/limitations. Benefits related to patient safety and workforce efficiency, and included GPs' ability to access and modify residents' MARs remotely, no need for nurses to fax orders to the pharmacy, and no need for pharmacy transcription of GPs' handwritten orders to create electronic MARs. Barriers and limitations related to inefficiency, low GP uptake and training/support, and included slower prescribing compared to written orders, the need for GP-signed paper copies of the MAR, lack of integration with GP clinic software, and low GP motivation to use the system, especially GPs with few patients at the RACF. GPs, nurses and pharmacists felt the ePMMS improved medication-safety and workforce-efficiency, however a number of barriers were identified that contributed to low GP-uptake and limited the benefits.


A pilot study on the effect of topical negative pressure on quality of life.
To discover the impact of topical negative pressure (TNP) on quality of life. An exploratory prospective cohort study was conducted on 26 patients undergoing TNP. The Cardiff Wound Impact Schedule (CWIS), a wound-specific tool, was used to investigate quality-of-life scores before therapy and four weeks after therapy or at wound closure. Wound dimensions were measured at both assessments, and the values for the CWIS domains (physical symptoms, social functioning, well-being and overall quality of life) were investigated using parametric and non-parametric tests. The mean duration of TNP therapy was 3.3 +/- 1.7 weeks. Topical negative pressure therapy helped to achieve complete wound closure in 14 patients (54%), and there was a mean reduction in wound surface area from 52.2 cm2 (range 4-150) to 26.8 cm2 (0-120). While there was no significant change in quality of life in patients whose wounds healed (1 +/- 11.9), the physical-functioning domain improved in obese patients (20 +/- 21, p < 0.05) and worsened in ambulatory patients (-3 +/- 13, p < 0.05). The portableTNP system had no significant impact on quality of life (-3 +/- 16), while the global quality-of-life score worsened with surgical intervention (-0.5 +/- 2, p < 0.05). Although TNP aids wound closure in patients with complex wounds, in selected cases their quality of life can worsen. This is the first exploratory cohort study of its kind, and has identified an urgent need to validate the use of patient-based outcome measures in TNP therapy. Such data can be useful in allocating resources and justifying funding in wound care.


Naproxen and aspirin in acute musculoskeletal disorders: a double-blind, parallel study in patients with sports injuries.
Seventy-nine patients with injuries of less than 14-days' duration were treated with either 750 mg naproxen or 2 g acetylsalicylic acid daily for 7 days in a double-blind trial. A statistically significant improvement (p less than 0.001) was noted in both treatment groups in respect of tenderness on palpation, pain on movement and functional capacity. However, there were no significant differences between the groups. Fresh injuries were over-represented in the acetylsalicylic acid group (p less than 0.01), and when all patients were analyzed together, a significantly better treatment result was obtained the shorter the interval between injury and start of treatment. This might have influenced the results from this study. Fifteen side-effects were reported by 11 patients, 5 in the naproxen group and 6 in the acetylsalicylic acid group. None was serious, and only 2 patients interrupted the treatment for this reason. It is suggested that treatment with analgesics or anti-inflammatory drugs should start as early as possible after the injury.


Methods, Applications and Challenges in the Analysis of Interrupted Time Series Data: A Scoping Review.
Interrupted time series (ITS) designs are robust quasi-experimental designs commonly used to evaluate the impact of interventions and programs implemented in healthcare settings. This scoping review aims to 1) identify and summarize existing methods used in the analysis of ITS studies conducted in health research, 2) elucidate their strengths and limitations, 3) describe their applications in health research and 4) identify any methodological gaps and challenges. Scoping review. Searches were conducted in MEDLINE, JSTOR, PUBMED, EMBASE, CINAHL, Web of Science and the Cochrane Library from inception until September 2017. Studies in health research involving ITS methods or reporting on the application of ITS designs. Screening of studies was completed independently and in duplicate by two reviewers. One reviewer extracted the data from relevant studies in consultations with a second reviewer. Results of the review were presented with respect to methodological and application areas, and data were summarized using descriptive statistics. A total of 1389 articles were included, of which 98.27% (N=1365) were application papers. Segmented linear regression was the most commonly used method (26%, N=360). A small percentage (1.73%, N=24) were methods papers, of which 11 described either the development of novel methods or improvement of existing methods, 7 adapted methods from other areas of statistics, while 6 provided comparative assessment of conventional ITS methods. A significantly increasing trend in ITS use over time is observed, where its application in health research almost tripled within the last decade. Several statistical methods are available for analyzing ITS data. Researchers should consider the types of data and validate the required assumptions for the various methods. There is a significant methodological gap in ITS analysis involving aggregated data, where analyses involving such data did not account for heterogeneity across patients and hospital settings.


[Chromosomal changes in patients with acute dysentery and their relation to immunologic shifts].
The correlation between the dynamics of the occurrence of the class of lymphocytes without chromosomal associations and with two associating acrocentric chromosomes (CL0 + 2) and the course of the disease, as well as the development of immunity in patients with acute dysentery, has been detected. The positive correlation between the occurrence of CL0 + 2 and cell-mediated immunity reactions presupposes the possibility of using this cytogenetic characteristic for evaluating the cell-mediated immunoreactivity of lymphocytes. No essential changes in the frequency of chromosomal aberrations in lymphocytes have been found to occur at all periods of observation.


Listening bandwidths and frequency uncertainty in pure-tone signal detection.
The effect of frequency uncertainty on the detection of tonal signals in noise was studied using a modified probe-signal method. Widths of the listening bands used during detection were measured directly, allowing for an analysis that separates the effects of having to monitor multiple independent bands from those due to limited frequency resolution. Uncertainty was varied by beginning each trial with a cue consisting of one, two, or four randomly chosen, simultaneously presented tones. An expected signal, whose frequency matched one of the components in a cue, was presented on a majority of trials. However, on remaining trials, the signal was a probe, which meant that its frequency differed from one of the components in the cue by a constant ratio. Performance as measured in percent correct declined for probes at increasingly distant ratios from the expected values. The results were converted to dB using individual psychometric functions for expected signals and listening bands were fitted using the rounded exponential filter of Patterson et al. [J. Acoust. Soc. Am. 72, 1788-1803 (1982)]. The obtained bandwidths are comparable to those reported using notched-noise maskers, but there is a small but consistent increase in bandwidth with increased numbers of components in the cues. The primary results is that the effects due to uncertainty are well described by a 1-of-M orthogonal band model, which takes into consideration limitations of the detector, including the widths of the listening bands.


DNA BARCODING: Barcoding corals: limited by interspecific divergence, not intraspecific variation.
The expanding use of DNA barcoding as a tool to identify species and assess biodiversity has recently attracted much attention. An attractive aspect of a barcoding method to identify scleractinian species is that it can be utilized on any life stage (larva, juvenile or adult) and is not influenced by phenotypic plasticity unlike morphological methods of species identification. It has been unclear whether the standard DNA barcoding system, based on cytochrome c oxidase subunit 1 (COI), is suitable for species identification of scleractinian corals. Levels of intra- and interspecific genetic variation of the scleractinian COI gene were investigated to determine whether threshold values could be implemented to discriminate conspecifics from other taxa. Overlap between intraspecific variation and interspecific divergence due to low genetic divergence among species (0% in many cases), rather than high levels of intraspecific variation, resulted in the inability to establish appropriate threshold values specific for scleractinians; thus, it was impossible to discern most scleractinian species using this gene.


Services for adults who have experienced child sexual assault: improving agency response.
Adults who experienced child sexual assault are likely to be present in all parts of the health and welfare systems both as clients and as staff. Research studies and accounts by survivors indicate that their experiences of seeking help are often not positive. In failing to acknowledge and deal with the issue of childhood sexual assault for adult clients and to be aware of its correlation with current problems, the health and welfare system reflects the larger society by avoiding knowledge of the impact of violence and abuse on health and well-being. This paper begins with an overview of studies on the prevalence of childhood sexual assault in adult populations and in clinical populations and of literature on the long term consequences of child sexual assault. It goes on to consider, with particular reference to an Australian context, how service providers can respond to the needs of survivors within their own agencies and notes the resources they may need to do this well.


Chronic alterations in ovine maternal corticosteroid levels influence uterine blood flow and placental and fetal growth.
Previous work from this laboratory demonstrated that the elevation of maternal plasma corticosteroid concentrations during pregnancy is important for the support of fetal development. Reducing ovine maternal plasma cortisol concentrations to nonpregnant levels stimulates homeostatic responses that defend fetal blood volume. The present study was designed to test the hypothesis that chronic decreases or increases in maternal plasma cortisol concentration alter uterine and placental blood flow and morphology. Three groups of pregnant ewes and their fetuses were chronically catheterized and studied: ewes infused with cortisol (1 mg.kg(-1).day(-1); high cortisol), ewes adrenalectomized and underreplaced with cortisol (0.5 mg.kg(-1).day(-1); low cortisol), and control ewes. The normal increment in uterine blood flow between 120 and 130 days was eliminated in the low-cortisol ewes; conversely, uterine blood flow was increased in the high-cortisol group compared with the control group. Fetal arterial blood pressure was increased in the high-cortisol group compared with controls, but there was no increase in fetal arterial pressure from 120 to 130 days of gestation in the low-cortisol group. The fetuses of both low-cortisol and high-cortisol groups had altered placental morphology, with increased proportions of type B placentomes, and overall reduced fetal placental blood flow. The rate of fetal somatic growth was impaired in both low-cortisol and high-cortisol groups compared with the fetuses in the intact group. The results of this study demonstrate that maternal plasma cortisol during pregnancy is an important contributor to the maternal environment supporting optimal conditions for fetal homeostasis and somatic growth.


Energy costs of simulated stair climbing as a job-related task in fire fighting.
The purpose of this investigation was to determine the energy requirement of simulated stair climbing. Metabolic costs of climbing stairs in getting to the scene of a fire can be very demanding for fire personnel. Heart rate and oxygen consumption were measured on 17 fire fighters during each of three conditions: (1) stair climbing without fire-fighting uniform or equipment, (2) stair climbing with fire-fighting uniform and equipment, and (3) pedaling a bicycle ergometer in a graded maximal exercise test. These three conditions were designed to determine (1) baseline reference values, (2) actual work task measures, and (3) maximum reference values. Results showed that climbing stairs with an 8-inch rise at 60 steps per minute with fire fighter's uniform and equipment (86.5 pounds) for five minutes required heart rates to reach 95% (84 to 100) of maximum effort, and oxygen consumption measures were found to be 80% (63 to 97) of maximum. It was concluded for the personnel studied that the rate of energy cost of climbing a simulated staircase with uniform and equipment required an ability to consume at least 2.7 L of oxygen per minute and 39 mL/kg/min.


Compartmentation of Metabolism of the C12-, C9-, and C5-n-dicarboxylates in Rat Liver, Investigated by Mass Isotopomer Analysis: ANAPLEROSIS FROM DODECANEDIOATE.
We investigated the compartmentation of the catabolism of dodecanedioate (DODA), azelate, and glutarate in perfused rat livers, using a combination of metabolomics and mass isotopomer analyses. Livers were perfused with recirculating or nonrecirculating buffer containing one fully (13)C-labeled dicarboxylate. Information on the peroxisomal versus mitochondrial catabolism was gathered from the labeling patterns of acetyl-CoA proxies, i.e. total acetyl-CoA, the acetyl moiety of citrate, C-1 + 2 of β-hydroxybutyrate, malonyl-CoA, and acetylcarnitine. Additional information was obtained from the labeling patterns of citric acid cycle intermediates and related compounds. The data characterize the partial oxidation of DODA and azelate in peroxisomes, with terminal oxidation in mitochondria. We did not find evidence of peroxisomal oxidation of glutarate. Unexpectedly, DODA contributes a substantial fraction to anaplerosis of the citric acid cycle. This opens the possibility to use water-soluble DODA in nutritional or pharmacological anaplerotic therapy when other anaplerotic substrates are impractical or contraindicated, e.g. in propionic acidemia and methylmalonic acidemia.


Ambiguous genitalia, microcephaly, seizures, bone malformations, and early death: a distinct MCA/MR syndrome.
We report on two siblings with hypotonia, ambiguous genitalia, microcephaly, ptosis, microretrognathia, thin lips, seizures, absent ossification of pubic rami, and brain abnormalities at the MRI. The two siblings died at 5 and 8 months, respectively. Molecular analysis indicated that SOX9, ARX, and DHCR7 genes were normal. Comparative genomic hybridization (CGH)-array analysis performed on the younger boy indicated two notable deletions, one on paternally inherited chromosome 4, and one on maternally inherited chromosome 5. The same deletions were found in a normal sister. Differential diagnoses and the possibility of a hitherto unreported syndrome are discussed.


Reading the mind with a mask? Improvement in reading the mind in the eyes during the COVID-19 pandemic.
The necessity to wear facial masks in public during the COVID-19 pandemic generated a unique situation where the eyes' importance as a visual source of information about individuals' mental and emotional states greatly increased. In this study, we tested the hypothesis that experience in looking in interlocutor's eyes (as a result of mask-wearing) will be correlated with enhanced performance on "reading the mind in the eyes test" (RMET). To test this, 87 participants performed an online version of the RMET at 2 different timepoints: when the mandatory mask wearing rules were put in place and a month later. We found that reported tendency to look at interlocutors' eyes, combined with experience in interacting with other people wearing masks, explained individual differences in RMET performance. Moreover, we found that individual's tendency to look at interlocutors' eyes was correlated with change in performance in reading the mind in the eyes over this month. These results suggest that in addition to individual's interest and motivation in understanding other's mental state, continuous everyday experiences can result in an improved capacity for reading mental and emotional states by looking into individuals' eyes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Controlling conformations of conjugated polymers and small molecules: the role of nonbonding interactions.
The chemical variety present in the organic electronics literature has motivated us to investigate potential nonbonding interactions often incorporated into conformational "locking" schemes. We examine a variety of potential interactions, including oxygen-sulfur, nitrogen-sulfur, and fluorine-sulfur, using accurate quantum-chemical wave function methods and noncovalent interaction (NCI) analysis on a selection of high-performing conjugated polymers and small molecules found in the literature. In addition, we evaluate a set of nonbonding interactions occurring between various heterocyclic and pendant atoms taken from a group of representative π-conjugated molecules. Together with our survey and set of interactions, it is determined that while many nonbonding interactions possess weak binding capabilities, nontraditional hydrogen-bonding interactions, oxygen-hydrogen (CH···O) and nitrogen-hydrogen (CH···N), are alone in inducing conformational control and enhanced planarity along a polymer or small molecule backbone at room temperature.


[Vascular access survey in the Triveneto area: data analysis for the year 2017].
In 2017 the Italian Society of Nephrology operating in the Triveneto area investigated through a questionnaire, distributed to the various nephrological centers in the regions of Friuli Venezia Giulia, Trentino Alto Adige and Veneto, the differences concerning organizational models, choice of dialysis, creation and management of vascular access. The results emerging from the analysis of the collected data are presented.


CO2-Mediated Formation of Chiral Carbamates from meso-Epoxides via Polycarbonate Intermediates.
Carbon dioxide has attracted broad interest as a renewable C1 feedstock for efficient transformation into value-added organic chemicals; nevertheless, far less attention was paid to its stereochemically controlled catalytic fixation/conversion processes. Here, we report a new strategy for the selective synthesis of chiral carbamates from carbon dioxide via polycarbonate intermediates, which are formed by the desymmetric copolymerization of meso-epoxides using enantiopure dinuclear Co(III) catalyst systems with 99% enantioselectivity. Subsequent degradation reaction of the resultant polycarbonates with various primary or secondary amine nucleophiles can afford optically active carbamates, with the complete configuration retention of the two chiral carbon centers. Our accomplishment reported here opens up a new route to prepare a wide range of CO2-based carbamate scaffolds with excellent yields and 99% enantiomeric excess.


Intermittent preventive treatment of malaria in pregnancy: at the crossroads of public health policy.
The intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) has been a key component of the focused antenatal care package for nearly a decade, reducing the burden of low birthweight attributable to malaria in sub-Saharan Africa. However, SP has lost parasite sensitivity in many sub-Saharan locations during the same period, rendering its beneficial effect in IPTp debatable. Malaria transmission has also declined in some epidemiological settings. There is no evidence to suggest, however, that the risk of malaria in pregnancy without preventive measures has declined in the same locations. Thus, the urgency to identify efficacious drugs and/or new strategies to prevent malaria in pregnancy remains as great as ever. We summarise the results of recently published SP-IPTp studies from areas of high drug resistance and/or low malaria transmission. We also present the evidence for mefloquine and azithromycin-based combinations (ABCs), two leading drug options to replace SP in IPTp. We discuss optimal dosing for ABCs and their likely protection against several sexually transmitted and reproductive tract infections. We also summarise data from a diagnosis-based alternative to IPTp known as the intermittent screening and treatment (IST) for malaria. Clinical and operational research is urgently needed to compare birth outcomes achieved by IPTp with ABCs vs. IST using an efficacious antimalarial therapy.


Temporal trends in percutaneous coronary intervention outcomes among older patients in the United States.
New percutaneous coronary intervention (PCI) device technologies are often rapidly adopted into clinical practice, yet few studies have examined the overall impact of these new technologies on patient outcomes in community practice. In hopes of determining temporal trends in PCI outcomes, we used data from the Centers for Medicare & Medicaid Service's Chronic Condition Warehouse (n = 3,250,836) by comparing patient characteristics and rates of 3-year major adverse cardiac events (MACE) across the balloon angioplasty (POBA) era (01/1991-09/1995), the bare metal stent (BMS) era (02/1998-04/2003), and the drug-eluting stent (DES) era (05/2004-10/2006). The adjusted association between era and outcomes was determined with Cox proportional hazards modeling (POBA era as reference). Compared with the POBA era, patients undergoing PCI were significantly older and had more medical comorbidities, and the risk for 3-year MACE was significantly lower during the BMS and DES eras (BMS vs. POBA adjusted HR [95% CI]: 0.930 [0.926-0.935]; DES vs. BMS: 0.831 [0.827-0.835]). Compared with males, the adjusted risk for 3-year MACE among females was lower during the POBA era, but slightly higher during the BMS and DES eras. Across all three eras, patients ≥75 years of age had higher adjusted risk for MACE compared with younger patients, and the risk for revascularization was lower for both females and older patients. Despite its application in older and sicker Medicare beneficiaries, there has been a significant decrease in post-PCI MACE over time. The risk for death or myocardial infarction is higher among females and older patients compared with males and younger patients; therefore, future studies should focus on improving clinical outcomes in these high-risk subgroups.


Functional Interplay between Type I and II Interferons Is Essential to Limit Influenza A Virus-Induced Tissue Inflammation.
Host control of influenza A virus (IAV) is associated with exuberant pulmonary inflammation characterized by the influx of myeloid cells and production of proinflammatory cytokines including interferons (IFNs). It is unclear, however, how the immune system clears the virus without causing lethal immunopathology. Here, we demonstrate that in addition to its known anti-viral activity, STAT1 signaling coordinates host inflammation during IAV infection in mice. This regulatory mechanism is dependent on both type I IFN and IFN-γ receptor signaling and, importantly, requires the functional interplay between the two pathways. The protective function of type I IFNs is associated with not only the recruitment of classical inflammatory Ly6Chi monocytes into IAV-infected lungs, but also the prevention of excessive monocyte activation by IFN-γ. Unexpectedly, type I IFNs preferentially regulate IFN-γ signaling in Ly6Clo rather than inflammatory Ly6Chi mononuclear cell populations. In the absence of type I IFN signaling, Ly6Clo monocytes/macrophages, become phenotypically and functionally more proinflammatory than Ly6Chi cells, revealing an unanticipated function of the Ly6Clo mononuclear cell subset in tissue inflammation. In addition, we show that type I IFNs employ distinct mechanisms to regulate monocyte and neutrophil trafficking. Type I IFN signaling is necessary, but not sufficient, for preventing neutrophil recruitment into the lungs of IAV-infected mice. Instead, the cooperation of type I IFNs and lymphocyte-produced IFN-γ is required to regulate the tissue neutrophilic response to IAV. Our study demonstrates that IFN interplay links innate and adaptive anti-viral immunity to orchestrate tissue inflammation and reveals an additional level of complexity for IFN-dependent regulatory mechanisms that function to prevent excessive immunopathology while preserving anti-microbial functions.


Mars' surface radiation environment measured with the Mars Science Laboratory's Curiosity rover.
The Radiation Assessment Detector (RAD) on the Mars Science Laboratory's Curiosity rover began making detailed measurements of the cosmic ray and energetic particle radiation environment on the surface of Mars on 7 August 2012. We report and discuss measurements of the absorbed dose and dose equivalent from galactic cosmic rays and solar energetic particles on the martian surface for ~300 days of observations during the current solar maximum. These measurements provide insight into the radiation hazards associated with a human mission to the surface of Mars and provide an anchor point with which to model the subsurface radiation environment, with implications for microbial survival times of any possible extant or past life, as well as for the preservation of potential organic biosignatures of the ancient martian environment.


Innate Immune Response and Outcome of Clostridium difficile Infection Are Dependent on Fecal Bacterial Composition in the Aged Host.
Clostridium difficile infection (CDI) is a serious threat for an aging population. Using an aged mouse model, we evaluated the effect of age and the roles of innate immunity and intestinal microbiota. Aged (18 months) and young (8 weeks) mice were infected with C difficile, and disease severity, immune response, and intestinal microbiome were compared. The same experiment was repeated with intestinal microbiota exchange between aged and young mice before infection. Higher mortality was observed in aged mice with weaker neutrophilic mobilization in blood and intestinal tissue and depressed proinflammatory cytokines in early infection. Microbiota exchange improved survival and early immune response in aged mice. Microbiome analysis revealed that aged mice have significant deficiencies in Bacteroidetes phylum and, specifically, Bacteroides, Alistipes, and rc4-4 genera, which were replenished by cage switching. Microbiota-dependent alteration in innate immune response early on during infection may explain poor outcome in aged host with CDI.


[Prognostic value of bacteriological studies in peritonitis].
Based on multiple bacteriological assays of lymph and blood, it is concluded that single detection of pathogenic microorganisms in lymph and blood should not be considered an unfavourable prognostic sign. A provisional external drainage of the thoracic duct would reduce intoxication in patients with peritonitis, and it is estimated as a valuable prophylactic method of combating against bacteriemia.


Application of antimicrobial chitosan-Furcellaran-hydrolysate gelatin edible coatings enriched with bioactive peptides in shelf-life extension of pork loin stored at 4 and -20 °C.
In this study, the authors investigate the preservative capabilities of edible coatings comprising a blend of chitosan, furcellaran and gelatin hydrolysate enhanced with the bioactive peptides RW4 and LL37. The preservative effects on pork samples stored for 21 days at 4 °C and 6 months at -20 °C were studied, while examining changes in microbiological contamination, pH levels, water activity and sensory attributes. Microbiological analyses reveal the coatings' antimicrobial efficacy against aerobic bacteria, microscopic fungi and yeasts, particularly during the initial storage period, when coated samples exhibit microbial reductions of 0.5-2 log CFU/g compared to the controls. The coatings have no discernible impact on water activity during storage in refrigerated or freezer conditions. Notably, differences in pH development can be observed between the coated and control samples, potentially attributable to the antimicrobial action of the coatings. Sensory analysis allows to highlight the inhibition of deterioration related to sensory attributes through the use of edible coatings. In conclusion, employing bioactive peptide-enriched edible coatings holds promise for extending the shelf-life of perishable foods.


[Clinical and patho-anatomic aspects of metastases of breast cancer].
The importance of carcinoma of the breast in female malignancies demands a critical examination of the condition of metastases by means of certain clinical and pathological data. The clinical data and the results of autopsies of 384 patients with breast carcinoma were examined. The frequency and the chronology of occurrence of metastases put out metastases of lymphnodes , skeleton, lung, liver and local recurrences. The importance of the mediastinal lymph node metastases in the distribution of metastases in thoracical organs was established and is discussed. The relation of frequency of the metastases to primary tumour staging (TNM) shows a 63% rate of metastases in patients with No and 86% in patients with N+. A comparison of two decades (I = 1960-1969; II = 1970-1979) shows certain trends 1. In decade II more patients with primary stage T1-T2 NoMo were found in autopsies having less metastases. 2. More local recurrences and metastases of genital organs were diagnosed. 3. In decade II more "late-metastases" (2-10 years after primary diagnosis) were found. These developments are explained by better primary diagnostic methods, more frequent follow-up examinations after primary therapy, and more frequent application of secondary therapies (chemotherapy, radiotherapy).


Overlapping splicing regulatory motifs--combinatorial effects on splicing.
Regulation of splicing in eukaryotes occurs through the coordinated action of multiple splicing factors. Exons and introns contain numerous putative binding sites for splicing regulatory proteins. Regulation of splicing is presumably achieved by the combinatorial output of the binding of splicing factors to the corresponding binding sites. Although putative regulatory sites often overlap, no extensive study has examined whether overlapping regulatory sequences provide yet another dimension to splicing regulation. Here we analyzed experimentally-identified splicing regulatory sequences using a computational method based on the natural distribution of nucleotides and splicing regulatory sequences. We uncovered positive and negative interplay between overlapping regulatory sequences. Examination of these overlapping motifs revealed a unique spatial distribution, especially near splice donor sites of exons with weak splice donor sites. The positively selected overlapping splicing regulatory motifs were highly conserved among different species, implying functionality. Overall, these results suggest that overlap of two splicing regulatory binding sites is an evolutionary conserved widespread mechanism of splicing regulation. Finally, over-abundant motif overlaps were experimentally tested in a reporting minigene revealing that overlaps may facilitate a mode of splicing that did not occur in the presence of only one of the two regulatory sequences that comprise it.


Complexities of underground mining seismic sources.
This paper presents a numerical investigation on the influence of the mining environment on seismic sources, with a focus on pillar failure mechanisms in tabular mining. We investigate the influence of the mining stope (underground excavation or void) on seismic inversions for the scalar moment, corner frequency, source radius, stress drop and moment tensor using synthetic events created within elastodynamic numerical modelling software, WAVE3D. The main objective is to determine whether the source parameters calculated from the recorded waveforms are due to a combination of the stope source and the pillar sources, rather than being related only to crushing of the pillar or shearing in the pillar footwall. The main finding is that the presence of stopes, and types of pillars, have a significant impact on the seismic moment and other source parameters. This is important since the moment is viewed as a robust parameter on which seismic magnitude is often based; however, this study indicates that moments calculated for pillar failure in a tabular stoping environments are less representative of the shearing or crushing source than originally thought. This article is part of the theme issue 'Fracture dynamics of solid materials: from particles to the globe'.


Growth and Break-Up of Methanogenic Granules Suggests Mechanisms for Biofilm and Community Development.
Methanogenic sludge granules are densely packed, small, spherical biofilms found in anaerobic digesters used to treat industrial wastewaters, where they underpin efficient organic waste conversion and biogas production. Each granule theoretically houses representative microorganisms from all of the trophic groups implicated in the successive and interdependent reactions of the anaerobic digestion (AD) process. Information on exactly how methanogenic granules develop, and their eventual fate will be important for precision management of environmental biotechnologies. Granules from a full-scale bioreactor were size-separated into small (0.6-1 mm), medium (1-1.4 mm), and large (1.4-1.8 mm) size fractions. Twelve laboratory-scale bioreactors were operated using either small, medium, or large granules, or unfractionated sludge. After >50 days of operation, the granule size distribution in each of the small, medium, and large bioreactor sets had diversified beyond-to both bigger and smaller than-the size fraction used for inoculation. Interestingly, extra-small (XS; <0.6 mm) granules were observed, and retained in all of the bioreactors, suggesting the continuous nature of granulation, and/or the breakage of larger granules into XS bits. Moreover, evidence suggested that even granules with small diameters could break. "New" granules from each emerging size were analyzed by studying community structure based on high-throughput 16S rRNA gene sequencing. Methanobacterium, Aminobacterium, Propionibacteriaceae, and Desulfovibrio represented the majority of the community in new granules. H2-using, and not acetoclastic, methanogens appeared more important, and were associated with abundant syntrophic bacteria. Multivariate integration (MINT) analyses identified distinct discriminant taxa responsible for shaping the microbial communities in different-sized granules.


Characterization of multiple erythroid progenitors available in large quantity from rabbit marrow.
We have examined the characteristics of erythroid progenitors from rabbit marrow and assessed the potential of this species as a source from which substantial quantities of erythroid progenitors could be obtained. Plasma clot cultures of rabbit marrow demonstrate colonies consistent with erythroid colony forming units (CFUE) by day 2 and colonies resulting from two types of burst forming units (BFUE) seen on days 3 and 8-9, respectively. Characteristic colony morphologies were noted from each cell type as well as differential sensitivity to erythropoietin (Ep) with discrete maximum responses for each progenitor. Distinct buoyant density characteristics were noted when the precursors were subjected to isopyknic separation on linear density gradients of polyvinylpyrrolidone-coated silica. The total nucleated marrow cells obtained from each animal ranged from 1.7-4.7 X 10(9). The average yields for each progenitor wee 1.71(+/-0.43) X 10(7) for CFUE, 1.99(+/-0.36) X 10(6) for 3 day BFUE and 1.24(+/-0.11) X 10(6) for 8-9 day BFUE.


Photodynamic therapy results in induction of WAF1/CIP1/P21 leading to cell cycle arrest and apoptosis.
Photodynamic therapy (PDT) is a promising new modality that utilizes a combination of a photosensitizing chemical and visible light for the management of a variety of solid malignancies. The mechanism of PDT-mediated cell killing is not well defined. We investigated the involvement of cell cycle regulatory events during silicon phthalocyanine (Pc4)-PDT-mediated apoptosis in human epidermoid carcinoma cells A431. PDT resulted in apoptosis, inhibition of cell growth, and G0-G1 phase arrest of the cell cycle, in a time-dependent fashion. Western blot analysis revealed that PDT results in an induction of the cyclin kinase inhibitor WAF1/CIP1/p21, and a down-regulation of cyclin D1 and cyclin E, and their catalytic subunits cyclin-dependent kinase (cdk) 2 and cdk6. The treatment also resulted in a decrease in kinase activities associated with all the cdks and cyclins examined. PDT also resulted in (i) an increase in the binding of cyclin D1 and cdk6 toward WAF1/CIP1/p21, and (ii) a decrease in the binding of cyclin D1 toward cdk2 and cdk6. The binding of cyclin E and cdk2 toward WAF1/CIP1/p21, and of cyclin E toward cdk2 did not change by the treatment. These data suggest that PDT-mediated induction of WAF1/CIP1/p21 results in an imposition of artificial checkpoint at G1 --> S transition thereby resulting in an arrest of cells in G0-G1 phase of the cell cycle through inhibition in the cdk2, cdk6, cyclin D1, and cyclin E. We suggest that this arrest is an irreversible process and the cells, unable to repair the damages, ultimately undergo apoptosis.


Complete Repair of Osteonecrosis of the Femoral Head After Basicervical Femoral Neck Rotational Osteotomy: A Case Report.
We present a 28-year-old female patient who developed left hip pain and was diagnosed with osteonecrosis of the femoral head (ARCO stage II). The patient underwent a basicervical femoral neck rotational osteotomy (BFNRO) combining surgical hip dislocation technique and extended retinacular soft-tissue flap technique. She was followed up for 53 months and exhibited complete repair of the necrotic area, with normal hip range of motion, gait, and excellent hip functional scores. The BFNRO procedure, by rotating the necrotic area of the femoral head out of the weight-bearing zone, has the potential to achieve complete repair of the necrotic area.


Preventive effects of Bofutsushosan on obesity and various metabolic disorders.
Visceral fat accumulation has been reported as the most important risk factor for the development of various metabolic disorders. In this study, the preventive effects of Bofutsushosan, a Japanese Kampo preparation, on obesity and various metabolic disorders were investigated focusing on visceral fat accumulation using Tsumura, Suzuki, Obese, Diabetes (TSOD) mice, which showed significant accumulation of visceral fat, and developed metabolic disorders including glucose intolerance, hyperlipidemia, hypertension and hyperinsulinemia. At 2 months after initiation of the study, the control TSOD mice developed various metabolic disorders such as marked obesity and visceral fat accumulation, increases in the levels of blood glucose, insulin, total-cholesterol (TC) and triglyceride (TG), and abnormal glucose tolerance, hypertension and peripheral neuropathy as distinct from the control Tsumura, Suzuki, Non-Obesity (TSNO) mice, which do not develop obesity and various metabolic disorders. In the TSOD mice treated with Bofutsushosan, body weight gain and visceral/subcutaneous fat accumulation were significantly suppressed. Biochemical parameters in plasma (glucose, TC, insulin and tumor necrosis factor-alpha (TNF-alpha) level) were significantly suppressed, and abnormal glucose tolerance, elevation of blood pressure and peripheral neuropathy accompanying progression of metabolic disorders were also significantly suppressed. On the other hand, in TSNO mice, Bofutsushosan showed no noteworthy impacts on most parameters except for an improvement of the lipid plasma level. The above results suggested that Bofutsushosan could be effective in preventing obesity and various metabolic disorders.


Characterizing the Analogy Between Hyperbolic Embedding and Community Structure of Complex Networks.
We show that the community structure of a network can be used as a coarse version of its embedding in a hidden space with hyperbolic geometry. The finding emerges from a systematic analysis of several real-world and synthetic networks. We take advantage of the analogy for reinterpreting results originally obtained through network hyperbolic embedding in terms of community structure only. First, we show that the robustness of a multiplex network can be controlled by tuning the correlation between the community structures across different layers. Second, we deploy an efficient greedy protocol for network navigability that makes use of routing tables based on community structure.


How is sex considered in recent epidemiological publications on occupational risks?
Although women account for almost half the working population in industrialised countries, a sex bias persists in publications on medical research in general and occupational health in particular. The objective was to review recent publications on how sex is considered in epidemiological studies of occupational health, and to answer the following questions: are men and women studied equally, what are the respective characteristics of the studies which comprise only men, only women, and both, and what strategy of data analysis is chosen by the authors to take account of the sex factor in mixed studies. This review was based on publications in six journals during the year 1997, and included all the original articles reporting an epidemiological study of occupational health. In all, 348 articles were reviewed. In 40 articles (11%), the sex of the study population was not specified. In 177 articles (51%), the study population was mixed. In 108 (31%), the population consisted exclusively of men, and in only 23 (7%), exclusively of women. Even when study populations were mixed, they included fewer women than men. The sex composition of the population was related to the occupational risk factor considered, and also to health outcome. Industrial sector workers, and exposure to chemicals were more likely to be studied in samples of men. Mortality and health outcomes such as neoplasms and cardiovascular diseases were also more often studied among men. Surprisingly, study design differed significantly according to the sex of the population, and prospective studies, cohort studies, and exposed versus non-exposed studies were more often carried out in samples of men. Among the 177 mixed studies, sex was not investigated in over a quarter (27%). In 26 articles (15%), sex was not taken into account, but the authors attempted to justify this decision. In 46 mixed studies (26%), the results were adjusted for sex, and in 46 (26%), the authors gave separate results for men and women. In 11 studies (6%), more complete strategies of data analysis were chosen, including research for interactions or adjustment, followed by stratification. This review of recent publications in occupational health epidemiology showed that women are still less often studied than men, and that the sex factor is not investigated in many mixed studies. The results therefore underline the need for further research on occupational hazards among women, and on sex differences.


Depressive symptomatology among Namibian adolescent refugees.
Symptoms of depression have been considered rare in sub-Saharan populations. Using a standard assessment measure of depressive symptomatology, the Beck Depression Inventory, the prevalence of symptoms of depression was obtained from a group (N = 56) of Namibian refugees residing in a sub-Saharan host country. Contrary to expectations, the rates of self-reported symptoms were quite frequent, with many symptoms reported as moderate or severe by a large proportion of these youths. Using a stress model to explore these data, it was demonstrated that social support ameliorated the effects of chronic stress, as represented by the length of time in exile. It is argued that adaptation, acculturation, and adolescent developmental demands result in self-reports of depressive symptoms. These demands, however, are lessened in intensity by a strong social support system that is especially helpful early in the exile period.


Fortification of Breast Milk With Preterm Formula Powder vs Human Milk Fortifier in Preterm Neonates: A Randomized Noninferiority Trial.
Fortification of expressed breast milk (EBM) using commercially available human milk fortifiers (HMF) increases short-term weight and length in preterm very low-birth-weight (VLBW) neonates. However, the high cost and increased risk of feed intolerance limit their widespread use. Preterm formula powder fortification (PTF) might be a better alternative in resource-limited settings. To demonstrate that fortification of EBM by preterm formula powder is noninferior to fortification by HMF, in terms of short-term weight gain, in VLBW neonates. Open-label, noninferiority, randomized trial conducted from December 2017 to June 2019 at a level 3 neonatal unit in India. The trial enrolled preterm (born at or before 34 weeks of gestation) VLBW neonates receiving at least 100 mL/kg/d of feeds and consuming 75% of milk or more as EBM. Neonates were randomly assigned to receive fortification by either PTF or HMF. Calcium, phosphorus, iron, vitamin D, and multivitamins were supplemented in PTF and only vitamin D in the HMF group to meet the recommended dietary allowances. The primary outcome was the weight gain until discharge from the hospital or 40 weeks' postmenstrual age, whichever was earlier; the prespecified noninferiority margin was 2 g/kg/d. Secondary outcomes included morbidities such as necrotizing enterocolitis, feed intolerance, and extrauterine growth restriction (<10th percentile on the Fenton chart at 40 weeks' postmenstrual age). Of the 123 neonates enrolled, 60 and 63 were randomized to the PTF and HMF groups, respectively. The mean gestation (30.5 vs 29.9 weeks) and birth weight (1161 vs 1119 g) were comparable between the groups. There was no difference in the mean (SD) weight gain between the PTF and HMF groups (15.7 [3.9] vs 16.3 [4.0] g/kg/d; mean difference, -0.5 g/kg/d; 95% CI, -1.9 to 0.7). The lower bound of 95% CI did not cross the noninferiority margin. The incidence of feed intolerance was lower in the PTF group (1.4 vs 6.8 per 1000 patient-days; incidence rate ratio 0.19; 95% CI, 0.04 to 0.95), and fewer neonates required withholding of fortification for 24 hours or more (5% vs 22%; risk ratio, 0.22; 95% CI, 0.07 to 0.75). The incidence of necrotizing enterocolitis stage II or more (0 vs 5%) and extrauterine growth restriction (73% vs 81%) was comparable between the groups. Fortification with preterm formula powder is not inferior to fortification with human milk fortifiers in preterm neonates. Given the possible reduction in feed intolerance and lower costs, preterm formula might be a better option for fortification, especially in resource-restricted settings. Clinical Trial Registry, India Identifier: CTRI/2017/11/010593.


[ Modern condition and prospects of development of cardiac surgery in the Armed Forces].
Authors consider the problem of delivery cardiac surgical care to contingent of the Defence Ministry. Perspective directions of development of cardiac surgery in the Armed Forces of the Russian Federation are the development of minimally invasive cardio surgery, endovascular development of modern methods of diagnosis and treatment, further development of electrophysiological methods for diagnosis and treatment of disorders of rhythm and conduction, the introduction of various kinds of auxiliary mechanical circulatory support systems in acute and chronic heart failure, development of transplantation in cardiac surgery, improvement of algorithm selection and referral of patients requiring cardiac care by providing primary health care to troop central military medical institutions, creating a single register of cardiac patients as part of the Armed Forces in order to determine the order and place of treatment, etc.


Extracellular vesicle therapeutics from plasma and adipose tissue.
Extracellular vesicles (EVs) are cell-released lipid-bilayer nanoparticles that contain biologically active cargo involved in physiological and pathological intercellular communication. In recent years, the therapeutic potential of EVs has been explored in various disease models. In particular, mesenchymal stromal cell-derived EVs have been shown to exert anti-inflammatory, anti-oxidant, anti-apoptotic, and pro-angiogenic properties in cardiovascular, metabolic and orthopedic conditions. However, a major drawback of EV-based therapeutics is scale-up issues due to extensive cell culture requirements and inefficient isolation protocols. An emerging alternative approach to time-consuming and costly cell culture expansion is to obtain therapeutic EVs directly from the body, for example, from plasma and adipose tissue. This review discusses isolation methods and therapeutic applications of plasma and adipose tissue-derived EVs, highlighting advantages and disadvantages compared to cell culture-derived ones.


A check list of non-lichenised fungi occurring on Fagus crenata, a tree endemic to Japan.
Non-lichenised fungi from Fagus crenata, an endemic and major temperate tree species, were enumerated based on three approaches: fungarium specimens at the National Museum of Nature and Science; isolates obtained mainly from leaves and roots, and their molecular identification by barcoding region; and literature. In total, 209, 49, and 232 taxa were recognised from the fungarium specimens, isolates, and literature, respectively. Only three taxa were commonly observed using all three approaches. Moreover, the results demonstrate the diversity of fungi occurring on a single host plant species, and provide the basis for comparisons between fungi from Fagus spp. in other regions of the world.


MitoNEET-dependent formation of intermitochondrial junctions.
MitoNEET (mNEET) is a dimeric mitochondrial outer membrane protein implicated in many facets of human pathophysiology, notably diabetes and cancer, but its molecular function remains poorly characterized. In this study, we generated and analyzed mNEET KO cells and found that in these cells the mitochondrial network was disturbed. Analysis of 3D-EM reconstructions and of thin sections revealed that genetic inactivation of mNEET did not affect the size of mitochondria but that the frequency of intermitochondrial junctions was reduced. Loss of mNEET decreased cellular respiration, because of a reduction in the total cellular mitochondrial volume, suggesting that intermitochondrial contacts stabilize individual mitochondria. Reexpression of mNEET in mNEET KO cells restored the WT morphology of the mitochondrial network, and reexpression of a mutant mNEET resistant to oxidative stress increased in addition the resistance of the mitochondrial network to H2O2-induced fragmentation. Finally, overexpression of mNEET increased strongly intermitochondrial contacts and resulted in the clustering of mitochondria. Our results suggest that mNEET plays a specific role in the formation of intermitochondrial junctions and thus participates in the adaptation of cells to physiological changes and to the control of mitochondrial homeostasis.


Exosomes-based biomarker discovery for diagnosis and prognosis of prostate cancer.
African American men in the United States have higher incidence and mortality rates due to prostate cancer (PCa) compared to other races. In 2016 alone, nearly 30,000 cases of PCa in African American men were diagnosed and 4,450 men died from PCa. The underlying reasons for this health disparity in PCa are complex and include social, economic, and biologic determinants. To reduce or eliminate this health disparity, we must better understand the biology of the disease in African Americans and then develop novel diagnostic and prognostic biomarkers useful for timely and effective treatment decisions. Recently, there has been remarkable progress in understanding the role of exosomes (vesicles of 30-150 nm diameter) in cancer development and progression. Exosomes are loaded with unique cargo, including proteins, nucleic acids, lipids, and metabolites, that could predict the cells of their origin. Therefore, circulating exosomes in cancer patients are being used as a type of biopsy to identify novel biomarkers for early diagnosis, prognosis, and therapeutics. In this review, we discuss the promising use of exosomes to (a) identify race-related unique biological features of PCa, and (b) discover novel biomarkers for better diagnosis and prognosis of PCa, with the goal of reducing cancer health disparities.