Metagenomic characterization of swine slurry in a North American swine farm operation.
Modern day large-scale, high-density farming environments are inherently susceptible to viral outbreaks, inadvertently creating conditions that favor increased pathogen transmission and potential zoonotic spread. Metagenomic sequencing has proven to be a useful tool for characterizing the microbial burden in both people, livestock, and environmental samples. International efforts have been successful at characterizing pathogens in commercial farming environments, especially swine farms, however it is unclear whether the full extent of microbial agents have been adequately captured or is representative of farms elsewhere. To augment international efforts we performed metagenomic next-generation sequencing on nine swine slurry and three environmental samples from a United States of America (U.S.A.) farm operation, characterized the microbial composition of slurry, and identified novel viruses. We assembled a remarkable total of 1792 viral genomes, of which 554 were novel/divergent. We assembled 1637 Picobirnavirus genome segments, of which 538 are novel. In addition, we discovered 10 new viruses belonging to a novel taxon: porcine Statoviruses; which have only been previously reported in human, macaques, mouse, and cows. We assembled 3 divergent Posaviruses and 3 swine Picornaviruses. In addition to viruses described, we found other eukaryotic genera such as Entamoeba and Blastocystis, and bacterial genera such as Listeria, Treponema, Peptoclostridium and Bordetella in the slurry. Of these, two species Entamoeba histolytica and Listeria monocytogenes known to cause human disease were detected. Further, antimicrobial resistance genes such as tetracycline and MLS (macrolide, lincosamide, streptogramin) were also identified. Metagenomic surveillance in swine fecal slurry has great potential for novel and antimicrobial resistant pathogen detection.


Systemic lupus erythematosus patients contain significantly less igm against mono-methylated lysine than healthy subjects.
Post-translational modifications on proteins are important in biological processes but may create neo-epitopes that induce autoimmune responses. In this study, we measured the serum IgG and IgM response to a set of non-modified or acetyl- and methyl-modified peptides corresponding to residues 1-19 of the histone 3 N-terminal tail in systemic lupus erythematosus (SLE) patients and healthy subjects. Our results indicated that the SLE patients and healthy subjects produced antibodies (Abs) to the peptides, but the two groups had different Ab isotype and epitope preferences. Abs to the non-modified form, H31-19, were of the IgG isotype and produced by SLE patients. They could not recognize the scrambled H31-19, which contained the same amino acid composition but a different sequence as H31-19. In comparison, healthy subjects in general did not produce IgG against H31-19. However, about 70% of the healthy subjects produced IgM Abs against mono-methylated K9 of H31-19 (H31-19K9me). Our further studies revealed that ε-amine mono-methylated lysine could completely inhibit the IgM binding to H31-19K9me, but lysine had no inhibitory effect. In addition, the IgM Abs could bind peptides containing a mono-methylated lysine residue but with totally different sequences. Thus, mono-methylated lysine was the sole epitope for the IgM. Interestingly, SLE patients had much lower levels of this type of IgM. There was no obvious correlation between the IgM levels and disease activity and the decreased IgM was unlikely caused by medical treatments.We also found that the IgM Abs were not polyreactive to dsDNA, ssDNA, lipopolysaccharide (LPS) or insulin and they did not exist in umbilical cord serum, implying that they were not natural Abs. The IgM Abs against mono-methylated lysine are present in healthy subjects but are significantly lower in SLE patients, suggesting a distinct origin of production and special physiological functions.


[Treatment of intraocular metastatic tumors].
Analysis of the clinical picture of intraocular metastatic tumors and the results of the treatment with various methods. Between 1994-1997 intraocular metastatic tumors were diagnosed in 14 patients (19 eyes). There were 13 females and 1 male, aged 28 to 69 years (average 50). The primary tumor in 8 patients developed in the breast, in 4 cases in the lungs, 1 in the brain, and 1 in the kidney. In all patients the primary tumor was excised, then chemotherapy was applied in 9 cases, radiotherapy in 3 cases, and hormonal treatment in 2 cases. In 7 patients the metastatic process concerned also other organs: bones, liver, lungs, hypophysis, and lymphatic glands. Metastases developed in 10 months to 11 years since the diagnosis and treatment of the primary tumor. Intraocular tumors were the most often located near the optic disc (8 cases), or near the macula (4 cases). There were usually flat tumors (in 12 cases < 5 mm in thickness), creamy white, sometimes with pigment clamping. In order, to confirm the diagnosis of the tumor, USG was always performed and in 8 cases fluorescein angiography. In all cases topical treatment was applied, which consisted of irradiation with ruthenium (106Ru) in 6 eyes (in 1 case two times), laser coagulation in 3 eyes, and thermotherapy (TTT) with diode laser in 4 eyes, combined treatment (106Ru + TTT) in 2 eyes, 106Ru and 125I brachytherapy in one eye. The dose of radiation for the apex of the tumor was 60-90 Gy (av. 65). The eyeball was enucleated in 3 patients, 4 patients received chemotherapy. 2 patients received hormonal therapy, applied together with the topical treatment. In the majority of cases (14 eyes), a flat scar or the significant decrease of the volume of the tumor was obtained. 8 patients died, two are currently observed, the remaining 4 do not come to the control examination, and there is no information as to their fate. Good results of the treatment encourage further application of brachy and thermotherapy in the treatment of intraocular metastatic tumors. It allows for the conservative treatment of the eyeball, and also useful visual acuity is retained often.


[Regulation of plant height by gibberellins biosynthesis and signal transduction].
Plant height is one of the most important agronomic traits that could affect both crop yield and quality. Among all the hormones, gibberellins are crucial to regulate plant height. Cloning and molecular mechanism research of the plant height genes associated gibberellins have extremely important value for the regulation of crop growth and agricultural production, and have been widely used in rice, wheat and other grain crops breeding. In order to promote utilization of gibberellins in fruit trees, flowers and other horticultural crops breeding, we reviewed the regulation of plant height by gibberellins biosynthesis and signal transduction at the molecular level in this paper.


Airway anesthesia with lidocaine for general anesthesia without using neuromuscular blocking agents in a patient with a history of anaphylaxis to rocuronium: a case report.
We experienced a case of induction of general anesthesia without using neuromuscular blocking agents (NMBAs) in a 40-year-old woman with a history of anaphylaxis immediately after the administration of anesthetics lidocaine, propofol, and rocuronium to perform endoscopic sinus surgery 2 years before. The skin test showed a positive reaction to rocuronium and cis-atracurium. We induced general anesthesia without using NMBAs after inducing airway anesthesia with lidocaine (transtracheal injection and superior laryngeal nerve block). Deep general anesthesia was maintained with end-tidal 4 vol% sevoflurane. Hypotension was treated with phenylephrine infusion. The operation condition was excellent, and patient recovered without complications after surgery. Airway anesthesia with local anesthetics may be helpful when we cannot use NMBAs for any reason, including hypersensitivity to NMBA and surgery that needs neuromuscular monitoring.


Immunohistochemical colocalization of G protein alpha subunits and 5-HT in the rectal gland of the cartilaginous fish Scyliorhinus canicula.
Serotonin [5-hydroxytryptamine (5-HT)] is an important neuromodulator involved in a wide range of physiological functions. The effects of serotonin are mediated by an extended family of receptors coupled to multiple heterotrimeric G-proteins, associated with cellular membrane. G proteins connect receptors to effectors and thus trigger intracellular signaling pathways. These cellular processes several regulate systemic functions such as embryonic development, gonadal development, learning and memory, and organismal homeostasis. Generally, elasmobranch fish dwell a hypersaline environment and utilize a specialized extrarenal salt secreting organ, the rectal gland, to face ionic homeostasis. In this study in addition to the morphological, histochemical and immunohistochemical description of the Scyliorhinus canicula rectal gland, for the first time, the presence of serotonin (5-HT), and distribution of different types of G protein alpha subunits (Gα o, Gα q/11, and Gα s/olf) has been investigated in the rectal gland epithelium by confocal immunofluorescence techniques. Colocalization G proteins and 5-HT in the secretory epithelium of the gland suggests serotonin acts as a hormone and involves G proteins in an autocrine-paracrine control of rectal gland homeostasis.


[Screening of apparently healthy people returning from "the tropics"].
Screening for imported parasites and infections in apparently healthy travellers and immigrants from the tropics is made more difficult by the lack of specificity and sensitivity of the standard investigations of blood and stools. Investigations must focus on parasites and infections prevalent in the area where the person has been. In the majority of people returned from the tropics, no infections or parasites are detected. However, some parasites, such as schistosomiasis, amoebae, and strongyloides, persist for many years and must be treated to prevent the development of serious complications at a later stage. The possibility of HIV infection and hepatitis should also be kept in mind when screening.


New Phenol Benzoate Cyanine Picolinium Salt Photoacid Excited-State Proton Transfer.
Steady-state and time-resolved fluorescence techniques were employed to study the excited-state proton transfer (ESPT) to water and D2O of a new photoacid, phenol benzoate cyanine picolinium salt (BCyP). We found that the ground-state pKa is about 6.5, whereas the excited-state pKa* is about -4.5. The ESPT rate constant, kPT, to water is ∼0.5 × 1012s-1 (τPT ≈ 2 ps) and in D2O the rate is 0.33 × 1012 s-1. We determined that the BCyP photoacid belongs to the third regime of photoacids, the solvent-controlled regime.


Using the Ghana malaria indicator survey to understand the difference between female and male-headed households and their prevention and testing for malaria among children under 5.
Globally, 94% of malaria deaths occur in sub-Saharan Africa, and children under age 5 account for 70% of malaria-related mortality in the region. This study sought to examine differences between female-headed households (FHHs) and male-headed households (MHHs) with regard to malaria prevention and testing among children under age 5 (U5) in Ghana. This cross-sectional study used publicly available data from the 2019 Ghana Malaria Indicator Survey (GMIS). Frequencies and descriptive statistics were calculated for all key variables. Bivariate analyses comparing FHHs and MHHs were conducted using t tests and Chi-square analysis. A P value of 0.05 was taken for statistical significance. Five thousand one hundred and eighty one household were identified, of which 1938 (37.4%) were female-headed and 3243 (62.6%) were male-headed. 51.7% of FHHs included a child U5, whereas 67.8% of MHHs included a child U5. MHHs were significantly more likely to own an ITN than FHHs (83.1% vs. 78.3%, P < 0.001), whereas FHHs were more likely to report taking malaria prevention steps such as spraying the house with insecticide, filling in stagnant puddles, and keeping surroundings clear (all significant at P < 0.001). U5 children in MHHs were more likely to sleep under a bed net the night preceding the survey (51.0%) than U5 children in FHHs (44.8%), although the finding was not statistically significant. The rates of fevers in the previous two weeks among children U5 were similar across MHH and FHH (24.2% vs. 22.3%), and the rates of testing for malaria among those who experienced a febrile episode were also similar across MHHs and FHHs (39.0% vs. 41.3%). Of those tested, the percentage of U5 children who tested positive for malaria was also similar across MHHs and FHHs (63.9% vs. 63.0%). Both FHHs and MHHs in Ghana make a concerted effort to prevent and test for malaria among children U5 in their households. Despite differences in malaria prevention strategies, there were no significant difference in febrile episodes, malaria testing, and rates of positivity, suggesting that malaria prevention is challenging for all households in Ghana. In the face of a newly-developed malaria vaccine, future research is warranted to ensure adequate uptake across all households.


Comparison of Grip Strength Measurements by Widely Used Three Dynamometers in Outpatients Aged 60 Years and Over.
Grip strength (GS) is widely used in various fields such as sports, rehabilitation, and geriatrics to assess muscle strength, and to diagnose sarcopenia and frailty in older adults. There is a potential for measurement differences among different dynamometers available, and studies comparing GS measurements by variable tools have conflicting results. The two most frequently used dynamometers are the Jamar hydraulic (Jamar) and spring-type hand grip dynamometers, and Jamar has not been compared to Jamar PLUS+ Digital (Jamar+) dynamometer in older adults. So, we aimed to assess GS measurements with the Jamar as the reference standard against Jamar+, and spring-type Takei T.KK. 5401 (Takei) digital dynamometers. One hundred and ten outpatients aged >60 years were included. Inter-instrumental reliability was determined. The differences between dynamometers were evaluated by Bland-Altman plots and measurement error. The measurements with Jamar+, and Takei dynamometers were reliable and valid regarding the Jamar dynamometer. Takei and Jamar+ dynamometers overestimated GS over the Jamar dynamometer. Though the differences in the measured values might be disregarded in clinical practice, individuals defined to have low GS varied by the use of different dynamometers. Grip strength better be measured by the same dynamometer in serial measurements of older individuals.


Metabolic responses produced by crude versus dispersed oil in Chinook salmon pre-smolts via NMR-based metabolomics.
Crude oil spills from tankers remain a serious threat along coastal California. Resource managers require information on the acute toxicity of treated and untreated oil, and their sublethal effects on wildlife. This investigation compared the toxic actions of the water-accommodated fraction (WAF) and the chemically-enhanced WAF (CEWAF; Corexit 9500) of Prudhoe Bay crude oil in pre-smolt Chinook salmon (Oncorhynchus tshawytscha) via nuclear magnetic resonance (NMR)-based metabolomics. Metabolite profiles from muscle samples, after 96h exposures, were measured using 1D (1)H NMR and compared via principal component analysis. It was determined that both WAF and CEWAF produced similar profiles in which amino acids, lactate and ATP comprised the highest intensity signals. Overall, metabolic substrates and growth measurements did not show residual effects of short-term exposure on long-term development. In conclusion, the 96h LC(50)s indicate dispersant application significantly decreased hydrocarbon potency and identified metabolites may be bio-indicators of hydrocarbon stress from hydrocarbon exposure.


Rediscovery and redescription of Laelaps lignicola G. & R. Canestrini, a remarkable myrmecophilous mite of the genus Cosmolaelaps Berlese (Acari: Mesostigmata: Laelapidae) from Italy.
Laelaps lignicola G. & R. Canestrini, 1882 is redescribed on the basis of numerous adults and deutonymphs, collected from Italy more than a century after its description. Despite its setiform setae without a discernible asymmetric swelling, this species fits the current concept of the genus Cosmolaelaps Berlese for all remaining diagnostic characters. Males of L. lignicola and Cosmolaelaps vacuus (Michael) share the presence of a basal process bearing seta av on telefemur II. This attribute is apparently not described in other laelapid mites. Also, males of L. lignicola are similar to those of some European species of Cosmolaelaps in having a distinct masticatory ridge on the fixed digit of chelicera. The ecological preference for decaying wood microhabitats, where L. lignicola is closely associated with Lasius emarginatus (Olivier) (Hymenoptera Formicidae), also suggests a close affinity with Cosmolaelaps species. Consequently, this species is provisionally placed in Cosmolaelaps and the new combination C. lignicolus (G. & R. Canestrini, 1882) comb. nov. is proposed.


The different roles of tryptophan transfer RNA in regulating trp operon expression in E. coli versus B. subtilis.
Escherichia coli and Bacillus subtilis use different mechanisms of sensing and responding to tryptophan and uncharged tRNA(Trp) as regulatory signals. In E. coli, tryptophan activates a repressor that binds to the trp promoter- operator, inhibiting transcription initiation. In B. subtilis, tryptophan activates an RNA-binding protein, TRAP, which binds to the trp operon leader RNA, causing transcription termination. In E. coli uncharged tRNA(Trp) accumulation stalls the ribosome attempting translation of tandem Trp codons in the leader-peptide coding region of the operon. This stalling permits the formation of an RNA antiterminator structure, preventing transcription termination. In B. subtilis uncharged tRNA(Trp) accumulation activates transcription and translation of the at operon. AT protein inhibits tryptophan-activated TRAP, thereby preventing TRAP-mediated transcription termination. These differences might reflect the unique organizational features of the respective trp operons and their ancestry.


What do individuals in different science groups within a life sciences organization think about genetic modification?
An assessment was undertaken of the attitudes of individuals within the science community towards a program to produce genetically modified cattle for altered milk composition, expectantly allowing for research into the treatment of multiple sclerosis in humans. The majority of respondents to an electronic survey expressed favorable attitudes to the program, thought it beneficial, respected individual freedom and was fair and just and disagreed that it was harmful. A passion for science and having a suitable lifestyle were the most important motivating factors for individuals. Finally, there were a wide range of responses to a number of cultural beliefs or myths. Science grouping significantly affected the responses. Compared with Systems and Land groups, Plant and Reproduction groups more strongly agreed with the project, thought it less harmful to interest groups, felt that genetic modification of animals was more morally acceptable, and more strongly agreed with the myth statements. These results indicate a diversity of beliefs and attitudes towards genetic modification amongst those within the science community, and highlight the importance of understanding ethics and myths in dealing with them. It is suggested that the diversity of beliefs could be better used to help shape public policy and understanding of biotechnology.


Dual-layers Raman reporter-tagged Au@Ag combined with core-satellite assemblies for SERS detection of Zearalenone.
Zearalenone (ZEN) is a prevalent mycotoxin identified in corn. A SERS-based immunosensor by constructing core-satellite assemblies was developed for ZEN detection. ZEN monoclonal antibody modified gold nanostars (AuNSs) were fabricated as the capture probe (core). The Raman signal probes (satellites) utilized ZEN antigen linked to the core-shell structures loaded with two layers of Raman reporter molecules (AuMBA@AgMBANPs). The coupling between AuNSs and AuMBA@AgMBANPs can produce a poweful electromagnetic field, thus considerably amplifying the Raman signal. The detection range of ZEN for corn samples under the optimal conditions was 5 ∼ 400 μg/kg with a LOD of 3 μg/kg, which completely satisfying the requirement of maximum residual level (60 μg/kg). Moreover, the proposed SERS method was consistent with the HPLC-FLD method for the detection of ZEN in naturally contaminated corn samples (90.58% ∼ 105.29%). Conclusively, fabricated immunosensor with exceptional sensitivity and specificity broaden the application of SERS in mycotoxin detection.


Point of care lung ultrasound is useful when screening for CoVid-19 in Emergency Department patients.
Background CoVid-19 can be a life-threatening lung disease or a trivial upper respiratory infection depending on whether the alveoli are involved. Emergency department (ED) screening in symptomatic patients with normal vital signs is frequently limited to oro-nasopharyngeal swabs. We tested the null hypothesis that patients being screened for CoVid-19 in the ED with normal vital signs and without hypoxia would have a point-of-care lung ultrasound (LUS) consistent with CoVid-19 less than 2% of the time. Methods Subjects Subjects were identified from ED ultrasound logs. Inclusion criteria Age 14 years or older with symptoms prompting ED screening for CoVid-19. Exclusion criteria Known congestive heart failure or other chronic lung condition likely to cause excessive B lines on LUS. Intervention Structured blinded ultrasound review and chart review Analysis We used an exact hypothesis tests for binomial random variables. We also measured LUS diagnostic performance using computed tomography as the gold standard. Results We reviewed 77 charts; 62 met inclusion criteria. Vital signs were normal in 31 patients; 10 (32%) of these patients had LUS consistent with CoVid-19. We rejected the null hypothesis (p-value for bitest <0.001). The treating physicians' interpretation of their own point of care lung ultrasounds had a sensitivity of 100% (95% CI 75%, 100%) and specificity of 80% (95% CI 68%, 89%). Conclusion LUS has a meaningful detection rate for CoVid-19 in symptomatic emergency department patients with normal vital signs. We recommend at least LUS be used in addition to PCR testing when screening symptomatic ED patients for CoVid-19.


Enhanced formation of non-phenolic androgen metabolites with intrinsic oestrogen-like gene transactivation potency in human breast cancer cells: a distinctive metabolic pattern.
Breast cancer is a sex steroid hormone-dependent malignant neoplasia. The role of oestradiol in this malignancy has been well documented; however, the involvement of androgens has remained controversial. To determine the role of non-phenolic androgen metabolites in human breast cancer, we studied the metabolism of [(14)C] testosterone and [(14)C] androstenedione in oestrogen-dependent MCF-7 cells and non-oestrogen-dependent MDA-MB 231 cells, at different substrate concentrations (1-10 muM) and time periods (30 min-48 h). Cultured non-oestrogen-dependent HeLa and yeast cells served as controls. Metabolites were identified and quantified by reverse isotope dilution. A distinctive pattern of androgen metabolism was identified in MCF-7 cells, being the 5alpha-androstane-3alpha,17beta-diol (3alpha,5alpha-diol) and its 3beta epimer (3beta,5alpha-diol), the major conversion products of testosterone (48.3%), with 5alpha-dihydrotestosterone as intermediary. The formation of 3alpha,5alpha-diol and 3beta,5alpha-diol (diols) was substrate concentration- and time-dependent, and abolished by finasteride. In contrast, very little of any diol formation was observed in MDA-MB 231, HeLa and yeast cell incubations. Additional enzyme gene expression studies revealed an overexpression of 5alpha-steroid reductase type-1 in MCF-7 cells, as compared with MDA-MB 231 cells. The oestrogen-like activities of diols were assessed in HeLa cells co-transfected with expression vectors for alpha or beta subtypes of the human oestrogen receptor (hER) genes and for an oestrogen-responsive reporter gene. The results show that 3beta, 5alpha-diol and to a lesser extent 3alpha,5alpha-diol bind with high relative affinity to hERalpha and hERbeta. Both diols induced hER-mediated reporter gene transactivation in a dose-response manner, similar to that induced by oestradiol, though with lower potency, an effect that was abolished by ICI-182 780. Furthermore, 3beta,5alpha-diol and to lesser extent 3alpha,5alpha-diol induced MCF-7 cell proliferation. The overall results demonstrated that MCF-7 cells exhibit enhanced expression and activity of androgen-metabolising enzymes, leading to rapid and large diol formation, and provide evidence that these androgen metabolites exert a potent oestrogen-agonistic effect, at genomic level, in oestrogen-dependent breast cancer cells. The data suggest that diols may act as in situ intracrine factors in breast cancer and that its formation can be pharmacologically inhibited.


Structure and mode of action of a mosquitocidal holotoxin.
The crystal structure of the full mosquitocidal toxin from Bacillus sphaericus (MTX(holo)) has been determined at 2.5 A resolution by the molecular replacement method. The resulting structure revealed essentially the complete chain consisting of four ricin B-type domains curling around the catalytic domain in a hedgehog-like assembly. As the structure was virtually identical in three different crystal packings, it is probably not affected by packing contacts. The structure of MTX(holo) explains earlier autoinhibition data. An analysis of published complexes comprising ricin B-type lectin domains and sugar molecules shows that the general construction principle applies to all four lectin domains of MTX(holo), indicating 12 putative sugar-binding sites. These sites are sequence-related to those of the cytotoxin pierisin from cabbage butterfly, which are known to bind glycolipids. It seems therefore likely that MTX(holo) also binds glycolipids. The seven contact interfaces between the five domains are predominantly polar and not stronger than common crystal contacts so that in an appropriate environment, the multidomain structure would likely uncurl into a string of single domains. The structure of the isolated catalytic domain plus an extended linker was established earlier in three crystal packings, two of which showed a peculiar association around a 7-fold axis. The catalytic domain of the reported MTX(holo) closely resembles all three published structures, except one with an appreciable deviation of the 40 N-terminal residues. A comparison of all structures suggests a possible scenario for the translocation of the toxin into the cytosol.


Clinical and socio-economic impact of influenza and respiratory syncytial virus infection on healthy children and their households.
This prospective study compared the clinical and socio-economic impact of laboratory-confirmed influenza and respiratory syncytial virus (RSV) infection on healthy children and their families. Among 1,520 otherwise healthy children aged< 15 years attending the Emergency Department for acute conditions other than trauma, influenza viruses and RSV were found in 234 (15.4%) and 116 (7.6%; p<0.0001) patients, respectively. The fact that influenza has a similar global clinical impact on the community to that of RSV infection, but represents a greater socio-economic burden, may contribute to broadening the acceptance of influenza vaccination.


Comparative studies between mice molars and incisors are required to draw an overview of enamel structural complexity.
In the field of dentistry, the murine incisor has long been considered as an outstanding model to study amelogenesis. However, it clearly appears that enamel from wild type mouse incisors and molars presents several structural differences. In incisor, exclusively radial enamel is observed. In molars, enamel displays a high level of complexity since the inner part is lamellar whereas the outer enamel shows radial and tangential structures. Recently, the serotonin 2B receptor (5-HT2BR) was shown to be involved in ameloblast function and enamel mineralization. The incisors from 5HT2BR knockout (KO) mice exhibit mineralization defects mostly in the outer maturation zone and porous matrix network in the inner zone. In the molars, the mutation affects both secretory and maturation stages of amelogenesis since pronounced alterations concern overall enamel structures. Molars from 5HT2BR KO mice display reduction in enamel thickness, alterations of inner enamel architecture including defects in Hunter-Schreger Bands arrangements, and altered maturation of the outer radial enamel. Differences of enamel structure were also observed between incisor and molar from other KO mice depleted for genes encoding enamel extracellular matrix proteins. Thus, upon mutation, enamel analysis based exclusively on incisor defects would be biased. In view of the functional relationship between enamel structure and tooth morphogenesis, identification of molecular actors involved in amelogenesis requires comparative studies between mice molars and incisors.


Human exposure asseessment to different arsenic species in tea.
Inorganic forms of arsenic are much more highly toxic to humans than organic species. Their effects include being carcinogenic, genotoxic and neurotoxic, where in the latter case, above all, they affect nervous system development in the foetus, infants and children. The main foodstuffs contributing significantly to its total dietary intake are drinking water, rice (and its products), fish, seafood, cereals, seaweed, root vegetables, food supplements, mushrooms and tea. After water, tea is the second most popular beverage drunk in Poland with average consumption annually indicating that statistically every Polish inhabitant drinks at least one cup of tea daily. The aim of the study was to determine the total and inorganic content of arsenic in various black and green teas available on the market and thus to estimate consumer exposure to inorganic arsenic from this foodstuff. Analyses of total and inorganic arsenic were performed on 23 samples of black and green teas that consisted of tea leaves, teas in bags and granules, from various sources. The analytical method was hydride generation atomic absorption spectrometry (HGAAS), after dry ashing of samples and reduction of arsenic to arsenic hydride using sodium borohydride. In order to isolate only the inorganic forms of arsenic prior to mineralisation, samples were subjected to concentrated HCl hydrolysis, followed by reduction with hydrobromic acid and hydrazine sulphate after which triple chloroform extractions and triple 1M HCl re-extractions were performed. Exposure of adults was estimated in relation to the Benchmark Dose Lower Confidence Limit (BMDL05) as set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) that resulted in a 0.5% increase in lung cancer (3.0 μg/kg body weight (b.w.) per day). Green teas were found to be more highly contaminated with both total and inorganic arsenic than black teas. Contamination of black teas total and inorganic arsenic was mean: 0.058 mg/kg (median: 0.042 mg/kg, 90th percentile: 0.114 mg/kg), and 0.030 mg/kg, (median: 0.025 mg/kg, 90th percentile: 0.030 mg/kg) respectively. Whilst for the green teas, these were correspondingly mean total arsenic content: 0.134 mg/kg (median: 0.114 mg/kg, 90th percentile: 0.234 mg/kg) and inorganic arsenic, mean: 0.100 mg/kg (median: 0.098 mg/kg, 90th percentile: 0.150 mg/kg). The estimated average adult exposures to inorganic arsenic in black and green tea were less than 1% of the BMDL05. Green tea samples, with the highest measured inorganic arsenic, were found to cause an intake exceeding 0.5% of the BMDL05 value. However when the drinking water is also accounted for when teas are prepared, then the exposure from black and green tea becomes exceeding 0.7% and 1.3% of the BMDL05 value respectively. Findings thus demonstrate that drinking black or green teas does not pose a significant health threat to consumers, even though contaminations in some individual samples were significant. total arsenic, inorganic arsenic, tea consumption, exposure assessment.


Connective tissue diseases and pregnancy.
Connective tissue diseases (CTD) such as systemic lupus erythematosus diffuse or limited systemic sclerosis and numerous others affect women frequently during the childbearing period. Every pregnancy in a patient with CTD should be regarded as high-risk pregnancy, and requires intensive monitoring and immediate treatment of clinical problems. For these reasons, for women suffering from CTD, who are pregnant or who intend to become pregnant, an interdisciplinary setting addressing all aspects of rheumatology, ob-gyn and neonatalogy needs to be provided. This setting includes particular diagnostic tools and laboratory parameters prior to and during pregnancy as well as in the post-partal period. Aside overt organ dysfunction, key problems in pregnant CTD patients consist mainly of haemostaseological problems such as antiphospholipid antibodies, neonatal lupus erythematosus, congenital heart block and drug therapy of the underlying disease, which will be outlined in this review.


COVID-19 infection following influenza vaccine injection and its complications among nurses working in educational-medical hospitals of Ardabil in 2020.
Health care workers are one of the groups at risk of influenza. Currently, influenza vaccination is very important more than ever before. Influenza is evolutionarily similar to SARS-CoV-2, and they have some common epitopes and mechanisms. Thus reducing the severity of COVID-19 disease by influenza vaccination seems possible. Therefore, the aim of this study is to investigate the relationship between influenza vaccination and COVID-19 infection among clinical nurses. The present study is a prospective analysis of nurses working in educational-medical hospitals of Ardabil. In this study, two groups of nurses were considered as case and control groups. The collected data were analyzed using SPSS software and descriptive (mean, standard deviation and frequency) and analytical (Chi-square) tests. A total of 279 individuals were included in the study according to the research criteria. The maximum duration of the disease was one week in the control group and four weeks in the case group. Chi-square test showed that there was a significant difference in terms of disease duration between the two groups (P = 0.000). Chi-square test showed that there was a statistically significant difference in terms of disease treatment between the two groups (P = 0.000). Influenza vaccine reduces the incidence of COVID-19 and reduces the need for hospitalization in patients with this disease. However, due to the positive effects of influenza vaccine on COVID-19 and its low cost, it is recommended to inject influenza vaccine more than before.


Soybean flour asthma: detection of allergens by immunoblotting.
A 43-year-old woman developed asthma 6 years after beginning work in a food-processing plant in which soybean flour was used as a protein extender. Symptoms of sneezing, coughing, and wheezing would begin within minutes of exposure to soybean flour and resolve 2 hours after exposure ceased. Skin tests were positive to a soy extract prepared from the flour. Airway hyperreactivity was confirmed by a positive bronchial challenge to methacholine. Bronchial challenge with soybean flour produced an immediate increase in specific airway resistance from 5.0 to 22.7 L. cm of H2O/L/sec. There was no response to challenge with lactose. The patient's allergic response to soy-flour extract was further characterized by several immunologic methods. IgE binding to soy-flour protein by direct RAST was 5.98 times that of a normal control serum. The soy-flour extract was separated by dodecyl sulfate-polyacrylamide gel electrophoresis. Twenty-four protein bands were detected in the crude soy-flour extract. After immunoblotting and subsequent autoradiography, nine proteins with molecular weights ranging from 54,500 to 14,875 were found. Cross-reactivity studies with other legumes demonstrated apparent immunologic identity between a component in green pea extract and a soybean protein with a molecular weight of 17,000. The clinical significance of this cross-reactivity is not known. We conclude that in this case of occupational asthma to soybean flour, multiple allergens were involved. Immunoblotting may be useful in identifying the allergens involved in occupational asthma.


The spectral power coherence of the EEG under different EMF conditions.
The present study introduces the concept of spectral power coherence (SPC), which reflects the pattern of coordination of the four basic EEG bands (delta, theta, alpha, and beta) at a specific location of the brain. The SPC was calculated for the pre-stimulus EEG signal during an auditory memory task under different electromagnetic field (EMF) conditions (900 MHz and 1800 MHz). The results showed that delta rhythm is less consequential in the overall cooperation between the bands than the higher frequency theta, alpha and beta rhythms. Additionally, it has been shown that the radiation effect on SPC is different for the two genders. In the absence of radiation males exhibit higher overall SPC than females. These differences disappear in the presence of 900 MHz and are reversed in the presence of 1800 MHz.


Divided-dose kinetics of mefloquine in man.
The kinetics of mefloquine was investigated following oral divided-doses in 10 healthy Caucasian volunteers. They received 500 or 750 mg followed by 500 mg 8 h later. Unchanged mefloquine (M) and its carboxylic acid metabolite (MM) were measured in whole blood and plasma for 50 days by h.p.l.c. Maximum blood and plasma M concentrations of 1872 +/- 362 ng ml-1 (mean +/- s.d.) and 1900 +/- 434 ng ml-1, respectively, were found within 6-10 h after the second dose. The terminal plasma elimination half-life was 20.1 +/- 3.7 days (mean +/- s.d.) and the oral clearance was 22.3 +/- 6.7 ml h-1 kg-1 (mean +/- s.d.). Plasma concentrations of MM exceeded those of M by 2-3 fold within 2 days. The whole blood concentration of MM was lower than that in plasma but also exceeded the whole blood concentration of M.


The metabolic syndrome: role of skeletal muscle metabolism.
Skeletal muscle constitutes the largest insulin-sensitive tissue in the body and is the primary site for insulin-stimulated glucose utilization. Skeletal muscle resistance to insulin is fundamental to the metabolic dysregulation associated with obesity and physical inactivity, and contributes to the development of the metabolic syndrome (MS). The inability to efficiently take up and store fuel, and to transition from fat to glucose as the primary source of fuel during times of caloric abundance (high insulin) or scarcity (low insulin) has been termed metabolic inflexibility which contributes to a whole body metabolic dysregulation and cardiovascular risk. Potential mechanisms contributing to reduced insulin signaling and action in skeletal muscle includes adipose tissue expansion and increased inflammatory adipokines, increased renin-angiotensin-aldosterone system (RAAS) activity, decreases in muscle mitochondrial oxidative capacity, increased intramuscular lipid accumulation, and increased reactive oxygen species. Future research is focused upon understanding these and other potential mechanisms in order to identify therapeutic targets for reducing MS risk. Strategies will include adequate physical activity and maintaining a healthy weight, but may also require specific pharmacologic interventions.


Squamous cell carcinoma of both ears associated with hypercalcaemia.
A case is presented showing rapid destruction of both ears by squamous cell carcinoma. The patient was transiently hypercalcaemic and hypophosphataemic; these biochemical abnormalities disappeared after radiotherapy.


Nitsche's Method For Helmholtz Problems with Embedded Interfaces.
In this work, we use Nitsche's formulation to weakly enforce kinematic constraints at an embedded interface in Helmholtz problems. Allowing embedded interfaces in a mesh provides significant ease for discretization, especially when material interfaces have complex geometries. We provide analytical results that establish the well-posedness of Helmholtz variational problems and convergence of the corresponding finite element discretizations when Nitsche's method is used to enforce kinematic constraints. As in the analysis of conventional Helmholtz problems, we show that the inf-sup constant remains positive provided that the Nitsche's stabilization parameter is judiciously chosen. We then apply our formulation to several 2D plane-wave examples that confirm our analytical findings. Doing so, we demonstrate the asymptotic convergence of the proposed method and show that numerical results are in accordance with the theoretical analysis.


[Poultry meat production with varying densities in raising the broilers].
Tests were carried out at two densities of raising the broilers on productional premises--16.6 and 23.6 per 1 m2 of flooring. Both the prophylactic programme and the conditions of tending and feeding were one and the same on the premises used. Each one of these was supplied with a cell in which birds were kept at the same density value as that on the other premise. Thus, four groups were formed in all: I--broilers kept at the rate of 16.6 per sq. m, II--broilers raised on the premise at 23.6/m2, III--broilers kept in a cell at 16.6 on the same premise where the other birds were kept at 23.6, and IV--broilers kept at 23.6 per sq. m. on the premise where the rate concerning the other birds was 16.6. The basic integral indices of the production effectiveness as well as the bioconversion of the dietary amino acids were followed up. It was found that during the transitional period the lower productional results with the broilers raised at higher densities were due to the action of biotic factors, and, more specifically, to the changes in the homotypical reactions that were the result of the higher density of raising. In the summer season the pesimal effect produced was a complex one, including not only the biotic factors but also the unfavourable action of the temperature and humidity regime.


Chemical Leslie effect in a chiral smectic-C* film: Singular target patterns.
We analyze experimentally and theoretically the flows that develop around the core of a +1 disclination placed at the center of a freely suspended ferroelectric smectic-C^{★} film subjected to a flow of ethanol. We show that the c[over ⃗] director partially winds under the action of the Leslie chemomechanical effect by forming an imperfect target and that this winding is stabilized by flows which are induced by the Leslie chemohydrodynamical stress. We show moreover that there is a discrete set of solutions of this type. These results are explained in the framework of the Leslie theory for chiral materials. This analysis confirms that the Leslie chemomechanical and chemohydrodynamical coefficients are of opposite signs and of the same order of magnitude to within a factor of 2 or 3. A method for measuring the velocity field is also proposed, which does not require seeding the film with particles that can disturb the flows.


[Early laser intervention of hemangioma in facial and neck regions of infant].
The study was to evaluate the method of early laser intervention of hemangioma in facial and neck regions of infant. Between January 1999 and December 2006, twelve patients, aged 6 days to 3 months, with cutaneous hemangioma in facial and neck regions, were treated with laser, eight cases with Nd:YAG laser therapy and four cases with Venus laser therapy. Four cases with hemangioma in facial and neck regions of infant treated with oral corticosteroid were as control. The outcome was recorded with 1 to 6 years of follow-up. Total resolution was obtained in twelve patients with laser intervention. Atrophic scars occurred in eight patients with Nd:YAG laser therapy, without other complications, such as ulceration, life-threatening hemorrhage and et al. No scar occurred in four patients with Venus laser therapy. Recurrence was not seen in twelve cases with laser therapy with follow-up. Hemangiomas enlarged continuously in four cases with oral corticosteroid therapy. Early laser intervention is an excellent management of cutaneous hemangioma in facial and neck regions of infant.


Flow cytometric analysis of prolonged stress-dependent heterogeneity in bacterial cells.
When bacterial cells are subjected to stress, cellular and population characteristics can change significantly. Rapid acquisition of these properties of cells in their native physiological state is necessary in order to precisely interpret their survival modes. The multiparametric analytical capability of flow cytometry allows us to acquire these data instantaneously. In this study, the temporal cellular and population distribution analyzed by flow cytometry for periods >500 h under osmotic stress revealed that bacterial cells were diversified into more than seven different subpopulations that differed in their intracellular DNA levels. It was also revealed that individual subpopulations attained a final surviving mode devoid of any intermittent or interdependent stages within themselves. Hence, bacterial cells were subjected to rigorous spontaneous metastable (nonequilibrium) variations in their cellular and population characteristics before reaching an equilibrium state, which allowed them to prolong their survival under stress, as revealed by robust flow cytometric analysis, in their native physiological state(s).


Variations associated with disaggregation methods in DNA flow cytometry.
We investigated the variations in DNA ploidy by flow cytometry (FC) among cell suspensions acquired by different disaggregation methods from the same tumor specimens. Cell suspensions (n = 121) of 40 solid tumors were obtained by mechanical mincing (n = 33), enzymatic digestion (n = 19), in vitro fine needle aspiration (FNA) (n = 34) or scraping (n = 35) of the tumor tissues. Mechanical disaggregation gave the highest cell yield, whereas enzymatic digestion provided the best cell viability. The mean values for the G0/G1 coefficient of variation, DNA indices and percent S phase were not significantly different in cell suspensions obtained with the four methods. However, the yield of malignant cells ranged from 60.4 +/- 5.3% (SEM) (enzymatic) to 82.3 +/- 3.1% (scraping). Tissue aliquots of 32 tumors were disaggregated by three to four methods, and the combined results of DNA ploidy obtained from different cell preparations showed that 22 tumors were nondiploid, but concordance with an abnormal DNA peak was found in only 27.3% (6/22) of the DNA nondiploid tumors. Our results indicate that scraping tumor tissue appears to be the best method for DNA FC since it has the highest percentage (61.3) of DNA nondiploid clones. Also, we believe the multiple samplings may provide comprehensive information on the DNA ploidy of solid tumors.


Individualisation, personalisation and person-centredness in mental healthcare: a scoping review of concepts and linguistic network visualisation.
Targeted mental health interventions are increasingly described as individualised, personalised or person-centred approaches. However, the definitions for these terms vary significantly. Their interchangeable use prevents operationalisations and measures. This scoping review provides a synthesis of key concepts, definitions and the language used in the context of these terms in an effort to delineate their use for future research. Our search on PubMed, EBSCO and Cochrane provided 2835 relevant titles. A total of 176 titles were found eligible for extracting data. A thematic analysis was conducted to synthesise the underlying aspects of individualisation, personalisation and person-centredness. Network visualisations of co-occurring words in 2625 abstracts were performed using VOSViewer. Overall, 106 out of 176 (60.2%) articles provided concepts for individualisation, personalisation and person-centredness. Studies using person-centredness provided a conceptualisation more often than the others. A thematic analysis revealed medical, psychological, sociocultural, biological, behavioural, economic and environmental dimensions of the concepts. Practical frameworks were mostly found related to person-centredness, while theoretical frameworks emerged in studies on personalisation. Word co-occurrences showed common psychiatric words in all three network visualisations, but differences in further contexts. The use of individualisation, personalisation and person-centredness in mental healthcare is multifaceted. While individualisation was the most generic term, personalisation was often used in biomedical or technological studies. Person-centredness emerged as the most well-defined concept, with many frameworks often related to dementia care. We recommend that the use of these terms follows a clear definition within the context of their respective disorders, treatments or medical settings. Open Science Framework: osf.io/uatsc.


Chemistry and cosmology.
The simplest elements, hydrogen and helium, offer a remarkably rich chemistry, which has controlled crucial features of the early evolution of the universe. Theoretical models of the origin of structure (stars, galaxies, clusters of galaxies, etc.) now incorporate this chemistry in some detail. In addition to the origin of structure, cosmologists are concerned with observational tests of competing world models. Primordial chemistry may give rise to some of the earliest departures from thermodynamic equilibrium in the universe. These effects may be observable as broad-band spectroscopic distortions of the cosmic background radiation, which otherwise exhibits a nearly perfect blackbody spectrum. The chemical history of the expanding universe is followed through a detailed calculation of the evolution of the abundances of H, H+, H-, H2, H2+, H3+, and other minor species. It is shown that continuous absorption by the small concentration of H- can produce a distortion in the cosmic background spectrum with a maximum at a frequency near nu/c = 9 cm-1 (wavelength 1.1 mm). The predicted effect lies only a factor of 5 below current limits. Its detection would provide an important test of our understanding of the recombination epoch of the universe.


Predictive Ability of Conventional and Combined Apgar Scores versus Neonatal Resuscitation and Adaptation Score in Early Neonatal Assessment.
The aim of this study was to assess the Neonatal Resuscitation and Adaptation Score (NRAS) value compared with the conventional and combined Apgar scores in predicting neonatal morbidity and mortality. A prospective cohort study was conducted on 289 neonates delivered at the Menoufia University Hospital. Trained physicians measured conventional Apgar score, combined Apgar score, and NRAS for the neonates at 1 and 5 minutes after delivery in the delivery room. Admitted neonates were followed during their stay to detect any adverse outcomes. Morbidities such as the need for neonatal intensive care unit admission, mechanical ventilation, surfactant and inotropes administration, need for extensive phototherapy, intravenous immunoglobulin or exchange transfusion, anemia, metabolic acidosis, abnormal liver and kidney function tests, coagulopathies, hypoglycemia, development of seizures in the first 72 hours of life, and positive changes in cranial ultrasound were significantly higher in neonates who lie within low or moderate NRAS than conventional and combined Apgar scores (p < 0.05). As predictors of mortality, the low and moderate values of the NRAS had higher positive predictive values at 1 (73.91 and 30.61%) and 5 minutes (88.89 and 50.94%) than the conventional Apgar scores at 1 (49.18 and 20.53%), 5 minutes (81.25 and 41.27%) and the combined Apgar scores at 1 (35.63 and 12.45%) and 5 minutes (53.1 and 41.33%). Our study suggests that the NRAS is better than conventional and combined Apgar scores in predicting neonatal morbidity and mortality. Furthermore, a depressed 5-minute NRAS is more predictive of mortality than 1-minute score. · NRAS is better than conventional and combined Apgar scores in predicting neonatal morbidity.. · NRAS is more predictive of mortality than conventional and combined Apgar scores.. · A depressed 5-minute NRAS is more predictive of mortality than 1-minute score..


Decomposition and dipteran succession in pig carrion in central Argentina: ecological aspects and their importance in forensic science.
Data on the insect species associated with corpse decomposition are particularly important for estimation of the post-mortem interval (PMI) in forensic science because the PMI is based on the lifecycle and behaviour of necrophagous insects, among other measures. To determine the dipteran succession on pig carrion, four experiments, one in each season, were carried out during 2004 in a rural area of Córdoba, central Argentina. Two pigs (Sus scrofa L.) were used in each of the four experiments. At each time-point one pig was placed in the shade and the other under direct sunlight. Insects were collected daily during the first 4 weeks and thereafter every 2 or 3 days. Five stages of decomposition were observed and a total of 24 710 adult specimens were collected, belonging to the following eight families of Diptera: Calliphoridae; Muscidae; Sarcophagidae; Phoridae; Piophilidae; Fanniidae; Sphaeroceridae, and Anthomyiidae. All Calliphoridae collected in this study were considered to be of potential forensic importance because of their necrophagous behaviour and because their immature stages use carrion as a food source. Other species, such as Musca domestica L. and Ophyra aenescens (Wiedemann), were also considered to represent potential forensic indicators.


Changes in fused cells induced by hvj (sendai virus): relationship of morphological changes to endocytosis of the surface membrane.
Fused Ehlrich ascites tumor (EAT) cells induced by hemagglutinating virus of Japan (HVJ; Sendai virus) had an irregular shape, reflecting the shape of cell aggregates before fusion. During subsequent culture, the fused cells gradually took on a spherical form within 60 min. Examination of the fused cells revealed a vigorous endocytosis of the cell membrane during the morphological change. When EAT cells were treated with porphyrin derivatives, and the morphological change to a spherical form was inhibited, endocytosis of fused cells was also suppressed, suggesting that the change is closely associated with endocytotic activity. Further examination with porphyrin derivatives and hydrogen peroxide suggested that the inhibition of morphological change is due to the suppression of endocytosis by active oxygen species produced by these substances. Experiments using an endocytotic inhibitor, methylamine, indicated that endocytosis is essential for the morphological change that occurs in the fused cells.


TGFβ1 signaling protects chondrocytes against oxidative stress via FOXO1-autophagy axis.
The forkhead box O1 (FOXO1) transcription factor is a key regulator of autophagy. In chondrocytes, reduced FOXO1 expression with aging causes osteoarthritis due to dysfunction of autophagy, but the mechanisms underlying regulation of FOXO1 expression and the reduction in expression with aging remain unclear. We investigated the mechanism by which transforming growth factor β1 (TGFβ1) signaling regulates the FOXO1-autophagy axis. Expression of FOXO1 was measured in chondrocytes after TGFβ1 treatment. Immunohistochemistry was performed to estimate the levels of activin receptor-like kinase 5 (ALK5) and FOXO1 in the knee joints of young, middle-aged and old mice. The effects of the ALK5 inhibitor and SMAD3 or SMAD2 knockdown on FOXO1 expression were evaluated. The role of TGFβ1 in autophagy after hydrogen peroxide (H2O2) treatment was analyzed. The protective effect of TGFβ1 against H2O2 treatment was assessed by cell viability assay and TUNEL assay. TGFβ1 promoted the expression of FOXO1 mRNA and protein. Both ALK5 and FOXO1 expression decreased with aging. ALK5 inhibition and SMAD3 knockdown suppressed induction of FOXO1 expression by TGFβ1, whereas SMAD2 knockdown increased it. TGFβ1 promoted the expression of microtubule-associated proteins 1A/1B light chain 3B (LC3)-I protein via the SMAD3-FOXO1 pathway. Furthermore, under H2O2 treatment, TGFβ1 promoted expression of LC3-II. TGFβ1 pretreatment suppressed cell death of chondrocytes following H2O2 treatment, but this protective effect was abolished by FOXO1 knockdown. TGFβ1 protects chondrocytes against oxidative stress via the FOXO1-autophagy axis, and a reduction in ALK5 expression might cause reduced FOXO1 expression with aging.


[Insulin Lispro as an alternative for insulin Humulin U in the treatment of an obese gestational diabetic woman with allergy to Humulin U. Case report].
It has been reported the case of 32-year-old obese gestational diabetic woman, treated with Humulin U and Humalog from 28 week of gestation. Seventeen days after initiation of insulin Humulin U the woman developed allergic type I cutaneous changes. During the few minutes following injection of Humulin U, the local wheal-flare reactions accompanied by itching has been occurred. These symptoms have been disappeared after a few hours. Insulin Humulin U was discontinued (18 j). Glycemia were monitored every 1-2 hours between 8 pm-6 am. Glycemia were in normal range between 8 pm. till 5 am. We have observed increase of glycemia to 6.34 mmol/l between 5 am.-6 am. The therapy was converted to Humalog injected at 5 30 am with glycemic control one hour later. The glycemic control was very good till next dose of Humalog before breakfast. The doses of Humalog were systematically increased at 5.30 am depend on glycemia at 6.30 with highest doses in 37 week of pregnancy (30 j with 180 j a day). The good glycemic control was maintained till delivery (38 week of pregnancy). That method of therapy was good tolerated and was not strenuous in spite of necessity of early awakening. We suggest that in obese gestational diabetics ultra-short insulin preparation, analog of short acting human insulin (Humalog), injected at 5.30 am might be considered as a therapeutic alteration for long acting insulin injected at evening. This observation may be interesting especially in situations in which long acting insulin injected at evening must be discontinued.


Mechanical forces shaping the development of the inner ear.
The inner ear is one of the most complex structures in the mammalian body. Embedded within it are the hearing and balance sensory organs that contain arrays of hair cells that serve as sensors of sound and acceleration. Within the sensory organs, these hair cells are prototypically arranged in regular mosaic patterns. The development of such complex, yet precise, patterns require the coordination of differentiation, growth, and morphogenesis, both at the tissue and cellular scales. In recent years, there is accumulating evidence that mechanical forces at the tissue, the cellular, and the subcellular scales coordinate the development and organization of this remarkable organ. Here, we review recent works that reveal how such mechanical forces shape the inner ear, control its size, and establish regular cellular patterns. The insights learned from studying how mechanical forces drive the inner ear development are relevant for many other developmental systems in which precise cellular patterns are essential for their function.


Pharmacological induction of heat shock proteins ameliorates toxicity of mutant PKCγ in spinocerebellar ataxia type 14.
Amyloid and amyloid-like protein aggregations are hallmarks of multiple, varied neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. We previously reported that spinocerebellar ataxia type 14 (SCA14), a dominant-inherited neurodegenerative disease that affects cerebellar Purkinje cells, is characterized by the intracellular formation of neurotoxic amyloid-like aggregates of genetic variants of protein kinase Cγ (PKCγ). A number of protein chaperones, including heat shock protein 70 (Hsp70), promote the degradation and/or refolding of misfolded proteins and thereby prevent their aggregation. Here, we report that, in various SCA14-associated, aggregating PKCγ variants, endogenous Hsp70 is incorporated into aggregates and that expression of these PKCγ mutants up-regulates Hsp70 expression. We observed that PKCγ binds Hsp70 and that this interaction is enhanced in the SCA14-associated variants, mediated by the kinase domain that is involved in amyloid-like fibril formation as well as the C2 domain of PKCγ. Pharmacological up-regulation of Hsp70 by the Hsp90 inhibitors celastrol and herbimycin A attenuated the aggregation of mutant PKCγ in primary cultured Purkinje cells. Up-regulation of Hsp70 diminished net PKCγ aggregation by preventing aggregate formation, resulting in decreased levels of apoptotic cell death among primary cultured Purkinje cells expressing the PKCγ variant. Of note, herbimycin A also ameliorated abnormal dendritic development. Extending our in vitro observations, administration of celastrol to mice up-regulated cerebellar Hsp70. Our findings identify heat shock proteins as important endogenous regulators of pathophysiological PKCγ aggregation and point to Hsp90 inhibition as a potential therapeutic strategy in the treatment of SCA14.


Evaluation of malaria screening in newly arrived refugees to the United States by microscopy and rapid antigen capture enzyme assay.
Before an empiric malaria treatment program, >60% of Liberian refugees had malaria on arrival to Minnesota. We compared microscopy with rapid antigen testing for detecting asymptomatic parasitemia. Nine of 103 (8.7%) had malaria by polymerase chain reaction (blood smear and rapid testing had a sensitivity of 22%). The empiric treatment program has decreased the rate of imported asymptomatic malaria. Blood film and rapid antigen testing are poor screening tests.


Synthesis, DNA-binding and antiproliferative properties of acridine and 5-methylacridine derivatives.
Several acridine derivatives were synthesized and their anti-proliferative activity was determined. The most active molecules were derivatives of 5-methylacridine-4-carboxylic acid. The DNA binding properties of the synthesized acridines were analyzed by competitive dialysis and compared with the anti-proliferative activities. While inactive acridine derivatives showed high selectivity for G-quadruplex structures, the most active 5-methylacridine-4-carboxamide derivatives had high affinity for DNA but showed poor specificity. An NMR titration study was performed with the most active 5-methylacridine-4-carboxamide, confirming the high affinity of this compound for both duplex and quadruplex DNAs.


Volumetric and histochemical studies of the adrenal medulla of mouse after reserpine administration.
The effect of single and consecutive doses of reserpine on the morphology and cellular and nuclear sizes of adrenaline and noradrenaline cells in the adrenals of mice were compared with the normal controls receiving saline injections as a placebo. Adopting micrometric measurements for apparent cellular and nuclear diameters, the pooled mean volumes of adrenaline- and noradrenaline-secreting cells and nuclei were calculated. Normal controls, subjected to consecutive daily saline injections for a period of 2 weeks, presented an increase in the intensity of the chromaffin reaction and higher values of cellular and nuclear sized of both cell types than those receiving single saline injection. These findings are believed to be a result of increased cell activity due to the stress of repeated, regular daily handling and injections. The increased measurements of cellular and nuclear sized of both types of adrenomedullary cells are believed to be due to hypermetabolic activity of the cells, thus exceeding action of reserpine shown by the decreased intensity of chromaffin reaction. Mice receiving daily consecutive reserpine injections showed a decrease in the intensity of chromaffin reaction as well as cellular and nuclear sizes compared with their controls. This is attributed to a decrease in the catecholamine content of the adrenal medulla.


Using Artificial Intelligence to Better Predict and Develop Biomarkers.
Advancements in technology have improved biomarker discovery in the field of heart failure (HF). What was once a slow and laborious process has gained efficiency through use of high-throughput omics platforms to phenotype HF at the level of genes, transcripts, proteins, and metabolites. Furthermore, improvements in artificial intelligence (AI) have made the interpretation of large omics data sets easier and improved analysis. Use of omics and AI in biomarker discovery can aid clinicians by identifying markers of risk for developing HF, monitoring care, determining prognosis, and developing druggable targets. Combined, AI has the power to improve HF patient care.


Finished Genome Sequence of Escherichia coli K-12 Strain HMS174 (ATCC 47011).
Escherichia coli strain K-12 substrain HMS174 is an engineered descendant of the E. coli K-12 wild-type strain. Like its ancestor, it is an important organism in biotechnological research and is used in fermentation processes for heterologous protein production. Here, we report the complete genome sequence of E. coli HMS174 (ATCC 47011).


Real-World Data in Support of Short Sleep Duration with Poor Glycemic Control, in People with Type 2 Diabetes Mellitus.
Sleep duration (SD) has been associated with metabolic outcomes. Is there an independent association between short/long SD and glycemic control (GC) in type 2 diabetes mellitus (T2DM) outpatients, compared to intermediate SD? Employing up-to-date definitions of SD, we comprehensively considered, simultaneously, all known confounding/mediating factors that recently emerged in the literature: age, gender, diet, physical activity, obesity, night pain, nocturnal diuresis, sleep quality, chronotype, sleep apnea, depressive symptoms, alcohol, caffeine, tobacco, number of endocrinologist appointments, T2DM family history, and sleep medication. A cross-sectional study of 140 consecutive T2DM outpatients, ages 40-65, glycohemoglobin (HbA 1c ) goal ≤ 7. We searched for variables (including HbA1c) significantly associated with short (<6 hours) or long (>8 hours) SD, in comparison to intermediate SD (6-8 hours). Higher HbA1c levels increased the chance of belonging to the group that sleeps <6 hours (p ≤ 0.001). Better sleep quality, nocturnal diuresis, and morningness increased the chance of belonging to the group that sleeps >8 hours (p < 0.05). There is an independent association between short SD and elevated HbA1c, in real-world T2DM outpatients. Future interventional studies could evaluate weather consistent, long-term sleep extension, from <6 hours to 7-9 hours per 24 hours, improves GC in T2DM outpatients.


Ex vivo Trophoblast-specific Genetic Manipulation Using Lentiviral Delivery.
In this protocol report, we describe a lentiviral gene delivery technique for genetic modification of the rat trophoblast cell lineage. Lentiviral packaged gene constructs can be efficiently and specifically delivered to the trophoblast cell lineage of the blastocyst. The consequences of 'gain-of-function' and 'loss-of-function' blastocyst manipulations can be evaluated with in vitro outgrowth assays or following transfer to pseudopregnant rats.


[Clinical study on female obesity complicated with climacteric syndrome treated by acupuncture].
To explore the mechanism of acupuncture in treating obesity complicated with climacteric syndrome (OCCS). Thirty female OCCS patients were treated by acupuncture, combination of body and auricular acupuncture, according to the treating principle based on syndrome differentiation. The changes in symptoms, signs, obesity index, Kupperman index, vegetative nerve system equilibrium index (Y value), levels of estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), gonadotropin releasing hormone (GnRH), leptin (LP), insulin (INS), nitric oxide (NO), nitric oxide synthase (NOS) and insulin activation index (IAI) in patients were observed. The obesity index, Kupperman index, Y value, and levels of LH, FSH, GnRH, LP, and INS increased, while levels of E2, NO, NOS and IAI decreased in OCCS patients. After acupuncture treatment, in the same time of obtaining promising effect in reducing weight, reversing effect was shown in all the above-mentioned parameters (P < 0.05 or P < 0.01) . Acupuncture has favorable regulatory effect on Kupperman index, Y value, E2, LH, FSH, GnRH, NO, NOS, LP, INS and IAI in OCCS patients, its effect in improving the hypothalamic-pituitary-gonad axis, vegetative nerve function and vasomotor dysfunction, and adjusting the resistance to leptin and insulin may be the important mechanisms.


Marine ω-3 Polyunsaturated Fatty Acid and Fish Intake after Colon Cancer Diagnosis and Survival: CALGB 89803 (Alliance).
Background: Marine ω-3 polyunsaturated fatty acids (PUFAs), primarily found in dark fish, may prevent colorectal cancer progression, in part through inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2). However, data in humans are limited.Methods: We examined marine ω-3 PUFAs and fish intake and survival among 1,011 colon cancer patients enrolled in Cancer and Leukemia Group B 89803 between 1999 and 2001 and followed through 2009. Diet was assessed during and 6 months after chemotherapy. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free (DFS), recurrence-free (RFS), and overall survival (OS).Results: We observed 343 recurrences and 305 deaths (median follow-up: 7 years). Patients in the highest vs. lowest quartile of marine ω-3 PUFA intake had an HR for DFS of 0.72 (95% CI, 0.54-0.97; Ptrend = 0.03). Individuals who consumed dark fish ≥1/week versus never had longer DFS (HR 0.65; 95% CI, 0.48-0.87; P-value = 0.007), RFS (HR 0.61; 95% CI, 0.46-0.86; Ptrend = 0.007), and OS (HR 0.68; 95% CI, 0.48-0.96; Ptrend = 0.04). In a subset of 510 patients, the association between marine ω-3 PUFA intake and DFS appeared stronger in patients with high PTGS2 expression (HR 0.32; 95% CI, 0.11-0.95; Ptrend = 0.01) compared with patients with absent/low PTGS2 expression (HR 0.78; 95% CI, 0.48-1.27; Ptrend = 0.35; Pinteraction = 0.19).Conclusions: Patients with high intake of marine ω-3 PUFAs and dark fish after colon cancer diagnosis may have longer DFS.Impact: Randomized controlled trials examining dark fish and/or marine ω-3 PUFA supplements and colon cancer recurrence/survival are needed. Cancer Epidemiol Biomarkers Prev; 27(4); 438-45. ©2018 AACR.


Cranial electrotherapy stimulation treatment of cognitive brain dysfunction in chemical dependence.
Several studies have shown that cranial electrotherapy stimulation (CES) is useful in treating brain dysfunction associated with alcoholism. A double-blind study replicated the latest of these findings in 60 inpatients and extended them by treating individuals with alcoholism and other chemical dependencies. Treatment effects were assessed on three subscales of the WAIS that are clinical indicators of organic brain syndrome. No placebo effect was found. CES appears to be a valuable adjunct to rehabilitation programs for addicted persons and can effect changes in areas not addressed by other treatment modalities.


Characterization of natural suppressor cells in human bone marrow.
Natural suppressor (NS) cells, which exert nonspecific suppressive activity in an unprimed manner, have been found in mouse, rabbit and monkey bone marrow (BM). In the present study, we characterize NS cells in human BM. NS activity was found in a fraction of low density (1.055-1.065 g/ml) BM cells that had been depleted of T cells, B cells, and monocytes. The NS activity was significantly decreased by the depletion of CD34+ or CD33+ cells but not CD56+ cells. The NS activity was indeed detected in isolated CD34+ cells and further enriched in CD34+CD33+ cells. Hematopoietic progenitor cells committed to the myeloid lineage were also enriched in the CD34+CD33+ cells, which significantly correlated to the NS activity. From these findings, it is strongly suggested that NS activity in human BM is exerted by the myeloid hematopoietic progenitors. Since cell-to-cell contact was not necessary for the action, NS cells seemed to secrete soluble mediator(s). Transforming growth factor-beta 1 and leukemia inhibitory factor were, however, not the candidates, based on experiments using neutralizing antibodies.


Circadian variation in plasma theophylline concentrations during maintenance therapy with a sustained-release preparation in patients with obstructive airways disease.
Circadian variation in plasma theophylline concentrations was studied in eight patients with obstructive airways disease during regular 12-hourly dosing at 09.00 and 21.00 h with a sustained-release theophylline formulation. After regular dosing for a minimum period of 3 days, plasma concentration measurements were made at 09.00, 13.00, 21.00 and 01.00 h on 3 consecutive days and at more regular intervals during a complete 24 h period on day 4. On each day, theophylline concentrations for the first 4 h of the dosing interval were consistently higher during the day than at night. However, the differences were significant only at 13.00/01.00 h on day 2, and for each of the first 4 h on day 4. On day 4, following the dose at 21.00 h the mean peak plasma theophylline concentration occurred 6.9 +/- 0.8 h after dosing; in contrast, after the morning dose the mean peak concentration occurred at 4.5 +/- 0.8 h. However, the mean 'steady-state' concentrations during the two dose intervals were not significantly different. Thus circadian variations in plasma drug concentrations do occur in patients taking maintenance theophylline therapy: differing rates of absorption may account for the observed pattern.


Long-Term Administration of High-Fat Diet Corrects Abnormal Bone Remodeling in the Tibiae of Interleukin-6-Deficient Mice.
In this study, we aimed to evaluate the influence of diet-induced obesity on IL-6 deficiency-induced bone remodeling abnormality. Seven-week-old IL-6(-/-) mice and their wild type (WT) littermates were fed a standard diet (SD) or high-fat diet (HFD) for 25 weeks. Lipid formation and bone metabolism in mice tibiae were investigated by histochemical analysis. Both IL-6(-/-) and WT mice fed the HFD showed notable body weight gain, thickened cortical bones, and adipose accumulation in the bone marrow. Notably, the HFD normalized the bone phenotype of IL-6(-/-) mice to that of their WT counterpart, as characterized by a decrease in bone mass and the presence of an obliquely arranged, plate-like morphology in the trabecular bone. Alkaline phosphatase and osteocalcin expressions were attenuated in both genotypes after HFD feeding, especially for the IL-6(-/-) mice. Meanwhile, tartrate-resistant acid phosphatase staining was inhibited, osteoclast apoptosis rate down-regulated (revealed by TUNEL assay), and the proportion of cathepsin K (CK)-positive osteoclasts significantly increased in IL-6(-/-) mice on a HFD as compared with IL-6(-/-) mice on standard chow. Our results demonstrate that HFD-induced obesity reverses IL-6 deficiency-associated bone metabolic disorders by suppressing osteoblast activity, upregulating osteoclastic activity, and inhibiting osteoclast apoptosis.


HIV risk among female sex workers with different patterns of drug use behaviors in Southwest China: a cross-sectional study.
Although many researchers found that drug use behaviors significantly increased HIV risk, few of them investigated the association between HIV risk and different drug use behaviors among female sex workers (FSWs) in China. The current study examines demographic and behavioral risk factors as well as the infections of HIV, syphilis, and among a subgroup of FSWs who are injection drug users (IDU) or noninjection drug users (NIDU) in comparison to Hepatitis C Virus (HCV) nondrug users (non-DU). We conducted secondary analysis of the 2010 National Sentinel Surveillance (NSS) data from Guangxi China. A self-administered, standard behavioral surveillance survey was completed by a total of 12,622 FSWs recruited from Guangxi, China. The Guangxi 2010 NSS sample included 2.6% NIDU and 0.5% IDU. Compared to non-DU, IDU were more likely to report no condom use in the last sex act (aOR = 3.25, 95%CI = 1.65, 6.40), inconsistent condom use in the past month (aOR = 4.88, 95%CI = 2.66, 8.96), having an HIV testing (aOR = 2.48, 95%CI = 1.34, 4.58), infections of HIV (aOR = 42.60, 95%CI = 9.45, 192.06), syphilis (aOR = 4.13, 95%CI = 1.86, 9.16), and HCV (aOR = 74.54, 95%CI = 30.26, 183.61). NIDU had 2.89 times higher than non-DU to report a history of sexually transmitted disease and 26% less likely to report inconsistent condom use in the past month (p < 0.05). We called for tailored, accessible, and nonjudgmental drug treatments coupled with effective sexual risk reduction interventions to help FSWs with various drug use problems to reduce their vulnerability and susceptibility of HIV risk in China as well as other cultural settings.


[Effects of salt stress on the growth and the nitrate reductase activity in Thellungiella halophila].
The results showed that when Thellungiella halophila was treated with NaCl, the fresh and dry weight, the water content, the succulency of whole plant and the root/shoot ratio were decreased (Figs. 2-4, 7); the organic matter content in roots was increased and the inorganic matter content in roots was decreased, while those in shoots changed in the opposite direction (Fig. 6); osmotic adjustment ability, the Na+ content, the root activity were increased (Figs. 5, 7, 8); the nitrate reductase activity increased significantly; the O(-)(2*) content decreased at about NaCl 50 mmol/L but increased at about NaCl 100-400 mmol/L (Fig. 10). The micrographs of T. halophila leaf surface by scanning electron microscope (SEM) indicate that there is no salt gland or bladder on the surface of T. halophila (Fig. 1), so it is not a salt-secreting halophyte. The determination of growth parameters, the Na(+) content and Na(+) X-ray (Table 1) microanalysis of T. halophila indicate that T. halophila is not a salt-exclusing halophyte but it probability is a salt-dilution halophyte.


Clinical Findings, Treatments and Outcomes in Farm Animals with Vertebral Fractures or Luxations: 22 Cases (2006-2017).
The aim of this study was to describe the signalment, clinical presentation, diagnostic findings, medical and surgical treatment and outcome of 22 farm animals diagnosed with a vertebral fracture or luxation. Medical records of 22 farm animals (7 goats, 6 alpacas, 5 cattle, 3 sheep and 1 deer) were reviewed for signalment, history, presenting clinical signs and neurological examination findings, clinicopathological results, diagnostic imaging, final diagnosis, medical and surgical management, clinical progression and outcome. Animals' age ranged from 1 day to 15 years. Neurological examination findings included decreased motor function (20/22), recumbency (14/22), altered mentation (13/22), cranial nerve deficits (4/22) and lack of nociception (3/22). Lesions were localized to the atlanto-occipital region (2/22), C1 to C5 (7/22), C6 to T2 (4/22), T3 to L3 (3/22), and L4 to S1 (6/22). Diagnoses included vertebral fracture only (4/22), luxation only (5/22) or both vertebral fracture and luxation (13/22). In five cases, no therapy was attempted, while 12 cases were treated medically and five cases were treated surgically. Surgical interventions included manual reduction (n = 1); arthrodesis (n = 2); laminectomy (n = 1); and laminectomy with pin fixation, cerclage wire and polymethylmethacrylate bridging (n = 1). Five of the 22 cases survived to hospital discharge; two of these were treated surgically. The cervical region was most commonly affected. Prognosis for these injuries in farm animals is guarded.


(Ar-tpy)RuII(ACN)3: A Water-Soluble Catalyst for Aldehyde Amidation, Olefin Oxo-Scissoring, and Alkyne Oxygenation.
The synthetic chemists always look for developing new catalysts, sustainable catalysis, and their applications in various organic transformations. Herein, we report a new class of water-soluble complexes, (Ar-tpy)RuII(ACN)3, utilizing designed terpyridines possessing electron-donating and -withdrawing aromatic residues for tuning the catalytic activity of the Ru(II) complex. These complexes displayed excellent catalytic activity for several oxidative organic transformations including late-stage C-H functionalization of aldehydes with NH2OR to valuable primary amides in nonconventional aqueous media with excellent yield. Its diverse catalytic power was established for direct oxo-scissoring of a wide range of alkenes to furnish aldehydes and/or ketones in high yield using a low catalyst loading in the water. Its smart catalytic activity under mild conditions was validated for dioxygenation of alkynes to highly demanding labile synthons, 1,2-diketones, and/or acids. This general and sustainable catalysis was successfully employed on sugar-based substrates to obtain the chiral amides, aldehydes, and labile 1,2-diketones. The catalyst is recovered and reused with a moderate turnover. The proposed mechanistic pathway is supported by isolation of the intermediates and their characterization. This multifaceted sustainable catalysis is a unique tool, especially for late-stage functionalization, to furnish the targeted compounds through frequently used amidation and oxygenation processes in the academia and industry.


Dietary habits and oral health related behaviors in relation to DMFT indexes of a group of young adult patients attending a dental school.
The aim of the present study was to investigate the dietary habits and oral health related behaviors in relation to the dental health status in terms of decayed, missing and filled teeth (DMFT index) of a group of young adults attending to a dental school located in a major city in Turkey. A total of 416 young adults (247 females and 169 males) with an age range of 18-25 (Mean 23.2 sd 0.97) attending the Oral Diagnosis department participated in the study. The patients completed a questionnaire including questions about demographic factors, dietary habits and oral health related behaviors. Subsequently, the DMFT index and plaque index was calculated. Descriptive statistics, Mann Whitney U/ Kruskal Wallis Variance analysis, Chi-square/Fisher's Exact tests and multiple linear regression analysis were used for statistical analysis of the data when applicable. According to the results of the study, approximately 70% of the patients had regular main meals and a very high snacking rate (76.9%) was present. Although not at a high rate, most of the patients brushed their teeth regularly twice a day (44.2%) and approximately half used other hygiene aids in addition to brushing (43.8%). The median of the DMFT index was 5 and a majority of the patients had moderate plaque accumulation which could be seen with the naked eye (45.0%). Dental plaque had the most significant effect on the DMFT index. In conclusion, advice, including importance of regularity of main meals, decrease in snacking frequency, regular brushing twice a day and the use of other oral hygiene aids for the elimination of dental plaque would be helpful to enhance the dietary habits and oral health related behaviors of young adult Turkish patients.


Automated detection of covalent adducts to human serum albumin by immunoaffinity chromatography, on-line solution phase digestion and liquid chromatography-mass spectrometry.
A generic method for the detection of covalent adducts to the cysteine-34 residue of human serum albumin (HSA) has been developed, based on an on-line combination of immunoaffinity chromatography for selective sample pre-treatment, solution phase digestion, liquid chromatography and tandem mass spectrometry. Selective anti-HSA antibodies immobilized on agarose were used for sample pre-concentration and purification of albumin from the chemically produced alkylated HSA. After elution, HSA and HSA adducts are mixed with pronase and directed to a reaction capillary kept at a digestion temperature of 70 degrees C. The digestion products were trapped on-line on a C18 SPE cartridge. The peptides were separated on a reversed-phase column using a gradient of organic modifier and subsequently detected using tandem mass spectrometry. Modified albumin samples consisted of synthetically alkylated HSA by the reactive metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine (NAPQI), and using the alkylating agent 1-chloro-2,4-dinitrobenzene (CDNB) as reference. The resulting mixture of alkylated versus non-modified albumin has been applied to the on-line system, and alkylation of HSA is revealed by the detection of the modified marker tetra-peptide glutamine-cysteine-proline-phenylalanine (QCPF) adducts NAPQI-QCPF and CDNB-QCPF. Detection of alkylated species was enabled by the use of data comparison algorithms to distinguish between unmodified and modified HSA samples. The in-solution digestion proved to be a useful tool for enabling fast (less than 2 min) and reproducible on-line digestion of HSA. A detection limit of 1.5 micromol/L of modified HSA could be obtained by applying 10 microL of NAPQI-HSA sample.


Sports Action Recognition Based on Deep Learning and Clustering Extraction Algorithm.
This paper constructs a sports action recognition model based on deep learning (DL) and clustering extraction algorithm. For the input detection image frame, athletes' movements are detected through DL network, and then athletes' sports movements are fused. Moreover, it expands new knowledge and improves learning ability through automatic learning training set. The neural network (NN) is applied to the sample set containing images of nonathletes, and the negative training sample set is iteratively enhanced according to the generated false positives, and the results are optimized by clustering method. Simulation experiments show that compared with other algorithms, the clustering extraction algorithm in this paper has achieved superior performance in recognition rate and false alarm rate, and the recognition speed is faster. The aim is to extract the athletes' training postures through the analysis of sports movements, so as to assist coaches to train athletes more professionally and provide some reference for sports movement recognition.


Structural genomic variations and Parkinson's disease.
Parkinson's disease (PD) is the second most common neurodegenerative disease, whose prevalence is projected to be between 8.7 and 9.3 million by 2030. Until about 20 years ago, PD was considered to be the textbook example of a "non-genetic" disorder. Nowadays, PD is generally considered a multifactorial disorder that arises from the combination and complex interaction of genes and environmental factors. To date, a total of 7 genes including SNCA, LRRK2, PARK2, DJ-1, PINK 1, VPS35 and ATP13A2 have been seen to cause unequivocally Mendelian PD. Also, variants with incomplete penetrance in the genes LRRK2 and GBA are considered to be strong risk factors for PD worldwide. Although genetic studies have provided valuable insights into the pathogenic mechanisms underlying PD, the role of structural variation in PD has been understudied in comparison with other genomic variations. Structural genomic variations might substantially account for such genetic substrates yet to be discovered. The present review aims to provide an overview of the structural genomic variants implicated in the pathogenesis of PD.


Improvement after cerebellar injury achieved by coordination dynamics therapy.
Coordination dynamics therapy of changing intensity was administered at home for nearly 8 years (at the beginning at low intensity) to a patient who had suffered a severe injury of the cerebellum (and of the cerebrum). Motor functions improved markedly during the first year of rather intensive therapy (by 42%), but there was but little improvement in the 5 following years (by 27%). An intensive 3-week coordination dynamics therapy was administered after 4 years of quantified therapy at an up-to-date therapy place under optimal conditions. The motor functions improved strongly (by 29% in 13 days). Therapy under professional conditions was shown to be much more efficient (by the factor of 150 as quantified by low-load coordination dynamics values) than that at home. A comparable patient with a brain (cerebral) injury improved slightly more under optimal conditions (by the factor of 390). In the patient with the injury of the cerebellum, the largest improvement concerned speech and higher mental functions. The strong improvement during the 3-weeks of optimal therapy may have partly been due to the enhanced training of CNS symmetries. It thus seems that not only phase and frequency coordination between neuron firings has to be improved by the therapy, but also symmetries in CNS organization.


Venous infarction of the myocardium in a newborn child: an unusual effect of disseminated intravascular coagulation.
A case is described of disseminated intravascular coagulation in a premature female infant, with the unusual and predominating feature of myocardial infarction consequent upon coronary vein thrombosis.Some reference is made to the incidence of coagulation disorders in the newborn and to methods of histological diagnosis.


[Cyclopexy on cyclodialysis cleft guided by anterior segment optic coherence tomography].
Objective: To analyze the accuracy of cyclopexy on traumatic cyclodialysis cleft guided by anterior segment optic coherence tomography (AS-OCT). Methods: Fifty-six eyes of 56 consecutive patients[41 males, 15 females, with a mean age of (43.14±13.85) years]who diagnosed with traumatic cyclodialysis cleft confirmed by ultrasound biomicroscopy (UBM) and underwent cyclopexy surgery at Shanxi Eye Hosiptal from July 2013 to February 2016 were included in the study. Patients were measured with the AS-OCT system before cyclopexy. AS-OCT findings of the cyclodialysis clefts were recorded. Localizing and suturing the clefts was guided by AS-OCT imaging. Preoperative and postoperative visual acuity (VA), intraocular pressure (IOP) and anterior chamber depth (ACD) were recorded and analyzed. Results: Imaging of preoperative AS-OCT of the 56 eyes showed an annular ciliary body detachment, a cyclodialysis cleft and shallow anterior chamber. The ciliary body detachment detected by AS-OCT showed an echo free zone between the annular ciliary body and the sclera. The cyclodialysis cleft showed a new pathway between the anterior chamber and the suprachoroidal space. AS-OCT imaging showed that the extent of cyclodialysis clefts ranged from 30 degrees to 240 degrees, which had a 0 degree to 20 degrees difference compared with UBM imaging. Localizing and suturing of the cyclodialysis clefts was guided by AS-OCT imaging. The best corrected visual acuity (BCVA) was 0.21±0.17 at baseline and 0.29±0.21 at five days postoperatively. The initial and final BCVA showed a remarkable difference after treatment (t=-4.98, P<0.01). The mean intra-ocular pressure (IOP) was (8.33±2.29) mmHg before surgery and (15.40±2.34) mmHg at five days postoperatively. There was a significant difference of IOP between preoperative and postoperative period (t=-16.590, P<0.01). The mean ACD was (1.94±0.45) mm preoperatively and (2.69±0.44) mm at five days postoperatively. There was also a significant difference of ACD between preoperative and postoperative period (t=-10.276, P<0.01). The postoperative reexamination found that ciliary body detachment or cyclodialysis clefts was not observed in the 56 eyes by AS-OCT. Conclusions: As a non-invasive method, AS-OCT is accurate, correlating well with UBM in the examination of cyclodialysis cleft, and can localize the extent of clefts before cyclopexy.


NFkappaB decoy oligonucleotides.
Molecular therapy is emerging as a potential strategy for the treatment of inflammatory diseases. Decoy oligonucleotides (ONs) against NFkappaB, an inducible transcription factor that plays a critical role in several inflammatory/immune diseases, can specifically block the transcriptional activity of this transcription factor. The therapeutic potential of such decoy ONs has been investigated in several chronic inflammatory-based diseases. However, the clinical use of decoy ONs is strongly hampered by several issues, including low bioavailability, a short half-life and limited intracellular uptake. Both chemical modifications to ONs and the use of delivery systems have been investigated in order to overcome these limitations. This review summarizes the most meaningful studies on the preclinical and clinical application of decoy ONs against NFkappaB in different diseases, and highlights successful strategies that have overcome the pharmacokinetic issues associated with ONs.


Microenvironment of macula flava in the human vocal fold as a stem cell niche.
There is growing evidence that the cells in the maculae flavae are tissue stem cells of the human vocal fold mucosa, and that the maculae flavae are a candidate for a stem cell niche. The role of microenvironment in the maculae flavae of the human vocal fold mucosa was investigated. Anterior maculae flavae from six surgical specimens were cultured in a mesenchymal stem cell growth medium or a Dulbecco's modified Eagle's medium. Using mesenchymal stem cell growth medium, the subcultured cells formed a colony-forming unit, and cell division reflected asymmetric self-renewal. This indicates that these cells are mesenchymal stem cells or stromal stem cells in the bone marrow. Using Dulbecco's modified Eagle's medium, the subcultured cells showed symmetric cell division without a colony-forming unit. A proper microenvironment in the maculae flavae of the human vocal fold mucosa is necessary to be effective as a stem cell niche that maintains the stemness of the contained tissue stem cells.


Nicastrin controls aspects of photoreceptor neuron specification and differentiation in the Drosophila eye.
Nicastrin is a component of the Notch signaling pathway involved in proteolytic release of the Notch receptor intracellular domain. It has been postulated that intracellular Notch is required within the nucleus of fly eye progenitor cells to enhance (pro-neural enhancement) and then repress (lateral inhibition) transcription of pro-neural genes. We present here an analysis of Nicastrin function during eye development and find that Nicastrin is essential to early photoreceptor neuron development. Nicastrin mutant tissue displays neuronal loss or hyperplasia; these phenotypes can be rescued by targeted expression of an intracellular form of Notch. Thus, nuclear translocation of Notch and its direct regulation of gene expression appear to be critical to pro-neural enhancement as well as lateral inhibition. In addition, we show that Nicastrin as well as Notch are required to maintain normal R-cell morphology, because the nuclei of mutant photoreceptor neurons cannot maintain their proper position. Thus, Notch signaling plays a role, not only in cell fate specification, but also in differentiation of photoreceptor neurons.


Modified hydroxyethyl starch protects cells from oxidative damage.
This article describes the synthesis of novel starch-antioxidant conjugates, which show great potential for biomedical applications to protect cells from oxidative damage. These conjugates were synthesized by the modification of a hydroxyethyl starch (molecular weight=200,000g/mol) with various sterically hindered phenols that differ in radical scavenging activity. They possess substantial radical scavenging activity toward a model free radical. It was found that the polymer conjugate conformation depends on the antioxidant structure and degree of substitution. We constructed the complete conformational phase behavior for the polymers with increasing degrees of substitution from small-angle neutron scattering data. It was observed that the conjugate conformation changes are the result of water shifting from a thermodynamically favorable solvent to an unfavorable one, a process that then leads to compaction of the conjugate. We selected the conjugates that possess high substitution degree but still exhibit coil conformation for biological studies. The high efficiency of the conjugates was confirmed by different in vitro (hypotonic hemolysis of erythrocytes/osmotic resistance of erythrocytes and the change of [Ca(2+)]i inside freshly isolated cardiomyocytes) and in vivo (acute hemorrhage/massive blood loss) methods.


Prognostic significance of high nuclear grade in patients with pathologic T1a renal cell carcinoma.
A reliable prognostic indicator in patients with pathologic T1a renal cell carcinoma has not yet been fully elucidated. The aim of this study was to investigate the prognosis of pathologic T1a renal cell carcinoma cases with a special focus on pathological factors. The study population consisted of 338 patients diagnosed with solitary renal cell carcinoma at our hospital between 1996 and 2009. The relationship between disease progression and clinicopathologic features was analyzed retrospectively to determine if it affected recurrence and distant metastasis. The Fuhrman nuclear grade distribution between the tumors was 1, 2, 3 and 4 in 68 (20.1%), 242 (71.6%), 21 (6.2%) and 7 cases (2.1%), respectively. A total of 11 subjects were identified as having recurrent tumors (3.3%), 9 of whom had metastatic lesions. Multivariate analysis showed that the appearance of tumor Grade 3 and 4 (hazard ratio: 13.0, 95% confidence interval: 3.90-43.0, P < 0.001) was an independent risk factor for tumor recurrence, while no significant correlation was found between tumor recurrence and age, gender, tumor side, tumor size, surgical methods, histology, microvascular invasion or surgical margin status. The 5-year recurrence-free survival rate was 67.8% in patients with a high nuclear grade tumor, and 96.8% in their counterparts. High nuclear grade is possibly one of the most important prognostic factors for predicting tumor recurrence and metastasis after surgery in pathologic T1a renal cell carcinoma. Thus, careful follow-up may be required in patients with pathologic T1a renal cell carcinoma of a high nuclear grade.