Effects of the lichen Peltigera canina on Cucurbita pepo spp. pepo grown in soil contaminated by DDTs.
Lichens consisting of a symbiotic association of green algae or cyanobacteria and fungi are found in a variety of environmental conditions worldwide. Terricolous lichens, located in soils, affect the living and lifeless environment of the soil due to their effective secondary metabolite and enzymatic content. Terricolous lichens can increase the biological, chemical, and physical usefulness of soil. However, their effects in ensuring the bioavailability of contaminated soil are not known, especially on soil pollution caused by DDTs (p,p'-DDE, p,p'-DDD, p,p'-DDT). This research focuses on the effect of terricolous lichens on zucchini (Cucurbita pepo spp. pepo) grown in soil contaminated by DDTs, utilizing their secondary metabolite and enzymatic contents. Firstly, Peltigera canina, a terricolous lichen species, was added to soil contaminated by DDTs as powdered and intact thallus. After lichen addition to soil, zucchini was planted in. The oxidative stress and antioxidative enzyme activities of zucchini were measured. According to the results, P. canina treatments have a positive effect on the growth and development of zucchini, although oxidative stress was observed. Also, it was determined that powdered application had more effective results than intact thallus application.


A new sensitizer DVDMS combined with multiple focused ultrasound treatments: an effective antitumor strategy.
Sonodynamic therapy (SDT) was developed as a promising noninvasive approach. The present study investigated the antitumor effect of a new sensitizer (sinoporphyrin sodium, referred to as DVDMS) combined with multiple ultrasound treatments on sarcoma 180 both in vitro and in vivo. The combined treatment significantly suppressed cell viability, potentiated apoptosis, and markedly inhibited angiogenesis in vivo. In vivo, the tumor weight inhibition ratio reached 89.82% fifteen days after three sonication treatments plus DVDMS. This effect was stronger than one ultrasound alone (32.56%) and than one round of sonication plus DVDMS (59.33%). DVDMS combined with multiple focused ultrasound treatments initiated tumor tissue destruction, induced cancer cell apoptosis, inhibited tumor angiogenesis, suppressed cancer cell proliferation, and decreased VEGF and PCNA expression levels. Moreover, the treatment did not show obvious signs of side effects or induce a drop in body weight. These results indicated that DVDMS combined with multiple focused ultrasounds may be a promising strategy against solid tumor.


A pediatric perspective on liver transplantation.
Liver transplantation has revolutionized the field of pediatric hepatology. The present status of this therapy is reviewed in this article from a nonsurgical perspective.


[Construction of the eukaryote expression vector of human soluble tumor necrosis factor receptor].
Human soluble tumor necrosis factor receptor (sTNFR) can interfere with the biological functions of interleukin-1, which may be appropriate to the treatment of periodontitis. The eukaryote expression vector of the human sTNFR gene must be constructed prior to conducting transgene therapy of periodontitis. Both sTNFR gene and plasmid pcDNA 3.1 (+) DNA were digested with Kpn I and Xho I. After purification, the two fragments were ligated by TakaRa DNA Ligation Kit (Ver 2.0). This recombinant DNA was then transformed into E. Coli Competent Cells JM109 and positive clones were selected on the LB agarose plate containing ampicillin (80 microg/ul). Six single clones were indentified by double digestion with kpn I and xho I and two fragments with the size of 5.4 kb and 1.0 kb were produced as expected. The sTNFR gene was successfully inserted into the eukaryote expression vector plasmid pcDNA 3.1 (+) by recombination technology in vitro.


Intersectional sociodemographic and neurological relationships in the naming ability of persons with post-stroke aphasia.
Significant attention has been given to the role of brain function and disruption in determining performance on naming tasks among individuals with aphasia. However, scholarly pursuit of a neurological explanation has overlooked the fundamental cornerstone of individual health-the underlying social, economic, and environmental factors that shape how they live, work, and age, also known as the social determinants of health (SDOH). This study examines the correlation between naming performance and these underlying factors. Individual level data from the 2010 Moss Aphasia Psycholinguistic Project Database (MAPPD) was matched with the 2009-2011 Medical Expenditure Panel Survey (MEPS) using a propensity score algorithm based on functional, health, and demographic characteristics. Multilevel, generalized, nonlinear regression models were applied to the resulting data set to assess the correlation between the Boston Naming Test (BNT) percentile score and age, income, sex, race, household size, marital status, aphasia type, and region of residence. Poisson regression models with bootstrapped standard errors were used to estimate these relationships RESULTS: Discrete dependent variable estimation with non-normal prior specification included individual level (age, marital status, years of education), socioeconomic (family income), health (aphasia type), household (family size), and environmental (region of residence) characteristics. Regression results indicated that, relative to individuals with Wernicke's, individuals with Anomic (0.74, SE = 0.0008) and Conduction (0.42, SE = 0.0009) aphasia performed better on the BNT. While age at the time of testing was not significantly correlated, higher income level (0.15, SE = 0.0003) and larger family size (0.002, SE = 0.002) was associated with higher BNT score percentiles. Finally, Black persons with aphasia (PWA) (-0.0124, SE = 0.0007) had lower average score percentiles when other factors were held constant. The findings reported here suggest higher income and larger family size are associated with better outcomes. As expected, aphasia type was significantly associated with naming outcomes. However, poorer performance by Black PWA and individuals with low income suggests that SDOH can play a critical role (positive and negative) in naming impairment in some populations with aphasia.


[The inhibitory effect of anti-streptococcus mutans immunoglobulin of yolk on glucan synthesis of Streptococcus mutans].
To observe the inhibitory effect of anti-Streptococcus mutans Hen-egg-yolk (IgY) on glucan synthesis of Streptococcus mutans. Determine the glucan with anthrone method after using the different titer of IgY on S.mutans and S.sobrinus. The inhibitory effect of antibody on S.mutans and S.sobrinus synthesis glucan had a similar tendency. The effect of inhibit glucan synthesis was influenced by the titer of antibody. High titer with high inhibition. Begin with the group of 1:16 titer, the group of 1:2 titer showed the highest inhibition (P<0.05). The antibody can reduce synthesis of glucan from S.mutans and S.sobrinus.


The effect of laser-activated bleaching with 445 nm and 915 nm diode lasers on enamel micro-hardness; an in vitro study.
The appearance of the teeth is of great importance to patients, particularly tooth color. In recent years, tooth whitening has been one of the most popular ways to restore tooth color. Bleaching gels can be affected by heat, light or laser, which can improve its effects. This study intends to examine the effects of two different wavelengths of diode laser (445 & 915 nm) after the bleaching process, on the enamel micro-hardness. A total of 65 caries-free humans third molars were randomly divided into five groups (N = 13): first group: bleaching gel activated with 915 nm diode laser (1.5 W), second: bleaching gel activated with 915-nm (2.5 W), third: bleaching gel activated with 445-nm (1 W), fourth: bleaching gel activated with 445-nm (1.5 W), fifth (control group): bleaching gel without laser activation. Micro-hardness test (Vickers test) was performed before and after the treatment. The data were submitted to repeated measurement ANOVA and Tukey's HSD post hoc test (α = 0.05). Enamel micro-hardness did not change significantly in groups 3 and 4 but decreased in groups 1 and 2. Group 2 showed the most reduction in micro-hardness. There were no significant changes in the control group. According to the results of this study, 445 nm Diode laser did not reduce enamel micro-hardness, making it suitable for bleaching treatments. However, more studies are required to consider other factors, such as color changes and pulp temperature.


Electrolyte disorders associated with the use of anticancer drugs.
The use of anticancer drugs is beneficial for patients with malignancies but is frequently associated with the occurrence of electrolyte disorders, which can be hazardous and in many cases fatal. The review presents the electrolyte abnormalities that can occur with the use of anticancer drugs and provides the related mechanisms. Platinum-containing anticancer drugs induce hypomagnesemia, hypokalemia and hypocalcemia. Moreover, platinum-containing drugs are associated with hyponatremia, especially when combined with large volumes of hypotonic fluids aiming to prevent nephrotoxicity. Alkylating agents have been linked with the occurrence of hyponatremia [due to syndrome of inappropriate antidiuretic hormone secretion (SIADH)] and Fanconi's syndrome (hypophosphatemia, aminoaciduria, hypouricemia and/or glucosuria). Vinca alkaloids are associated with hyponatremia due to SIADH. Epidermal growth factor receptor monoclonal antibody inhibitors induce hypomagnesemia, hypokalemia and hypocalcemia. Other, monoclonal antibodies, such as cixutumumab, cause hyponatremia due to SIADH. Tyrosine kinase inhibitors are linked to hyponatremia and hypophosphatemia. Mammalian target of rapamycin inhibitors induce hyponatremia (due to aldosterone resistance), hypokalemia and hypophosphatemia. Other drugs such as immunomodulators or methotrexate have been also associated with hyponatremia. The administration of estrogens at high doses, streptozocin, azacitidine and suramin may induce hypophosphatemia. Finally, the drug-related tumor lysis syndrome is associated with hyperphosphatemia, hyperkalemia and hypocalcemia. The prevention of electrolyte derangements may lead to reduction of adverse events during the administration of anticancer drugs.


Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence.
DNA sequences complementary to the Torpedo californica electroplax mRNA coding for the alpha-subunit precursor of the acetylcholine receptor were cloned. The nucleotide sequence of the cloned cDNA indicates that the precursor consists of 461 amino acids including a prepeptide of 24 amino acids. Possible sites for acetylcholine binding and antigenic determinants on the alpha-subunit molecule are discussed.


Metallothionein induction in islets of Langerhans and insulinoma cells.
Isolated pancreatic islets from rat and mouse and the insulinoma cell lines, betaHC9 and RINm5F, were investigated to determine the regulation of metallothionein (MT). Dexamethasone (DEX) increased rat and mouse islet and insulinoma cell MT levels in a time- and concentration-dependent manner. Rat islet MT expression was increased with interleukin-1beta (IL-1beta), but not tumor necrosis factor-alpha (TNF). However, MT induction by IL-1beta and TNF was synergistic with DEX in rat islets and insulinoma cells. Mouse islet MT failed to respond to IL-1beta alone, although IL-1beta and TNF were synergistic. IL-1beta and TNF did not synergize with DEX for mouse islet MT induction. Zinc sulfate induced MT in rat islets but not mouse islets. MT messenger RNA levels were significantly increased in rat islets in response to DEX and IL-1beta plus DEX. The inducible nitric oxide synthase inhibitors N(G)-monomethyl-L-arginine and aminoguanidine failed to inhibit IL-1beta induced MT levels in insulinoma cells, and the nitric oxide generating agent sodium nitroprusside failed to significantly affect MT levels. Phorbol dibutyrate increased MT levels in rat islets and betaHC9 cells, but phorbol dibutyrate and IL-1beta effects were not additive. Transgenic MT-null and wild-type mouse islets had similar insulin contents, but basal and glucose-stimulated insulin release from MT-null islets were significantly lower than in wild-type islets. Blood glucose levels in MT-null mice were, however, slightly lower than those in wild-type mice. Thus, MT induction in pancreatic islets and beta-cells is regulated by cytokines and DEX, and protein kinase C activation may play a role. However, regulation of MT induction in mouse and rat islets differs. MT also appears to modulate insulin release from pancreatic islets.


Determination of selected α-keto acids in dried blood samples using HPLC with fluorescence detection.
The determination of α-keto acids derived from amino acids is currently the most reliable approach for the diagnosis of some congenital metabolic diseases. An HPLC method for the simultaneous measurement of selected α-keto acids in dried blood samples has been developed and evaluated. Blood spot samples from a group of healthy blood donors were collected onto #903 Specimen Collection Paper. Prior the separation, the α-keto acids were derivatized with 1,2-diamino-4,5-dimethoxybenzene to the corresponding 3-substituted-6,7-dimethoxy-2(1 H)-quinoxalinol derivatives. For the separation, a reverse-phase column LichroCart 125-4, Purospher RP-18e, 5 µm, was used. The mixture of 25% ACN in deionized water (mobile phase A) and 100% ACN (mobile phase B) were used for a gradient elution of α-keto acids derivatives. Analytical performance of this method is satisfactory for all α-keto acids. The intra-assay and inter-assay coefficients were below 10% and recoveries were close to 100%. We have developed relatively simple, rapid, selective and sufficiently sensitive HPLC method with fluorescence detection for the determination of selected α-keto acids in dried blood samples. The presented method is suitable for clinical testing purposes.


Genetic polymorphism in European and African sheep breeds reared in Hungary based on 48 SNPs associated with resistance to gastrointestinal parasite infection using KASP-PCR technique.
This pilot study used an alternative and economically efficient technique, the Kompetitive Allele-Specific Polymerase Chain Reaction (KASP-PCR) to examine 48 SNPs from 11 parasite-resistance genes found on 8 chromosomes in 110 animals from five sheep breeds reared in Hungary; Hungarian Tsigai, White Dorper, Dorper, Ile de France, and Hungarian Merino. Allele and genotype frequencies, fixation index, observed heterozygosity, expected heterozygosity, F statistic, and their relationship with the Hardy-Weinberg equilibrium (WHE) and the polymorphic information content (PIC) were determined, followed by principal component analysis (PCA). As much as 32 SNPs out of the 48 initially studied were successfully genotyped. A total of 9 SNPs, 4 SNPs in TLR5, 1 SNP in TLR8, and 4 SNPs in TLR2 genes, were polymorphic. The variable genotype and allele frequency of the TLRs gene indicated genetic variability among the studied sheep breeds, with the Hungarian Merino exhibiting the most polymorphisms, while Dorper was the population with the most SNPs departing from the HWE. According to the PIC value, the rs430457884-TLR2, rs55631273-TLR2, and rs416833129-TLR5 were found to be informative in detecting polymorphisms among individuals within the populations, whereas the rs429546187-TLR5 and rs424975389-TLR5 were found to have a significant influence in clustering the population studied. This study reported a moderate level of genetic variability and that a low to moderate within-breed diversity was maintained in the studied populations.


N-(4-Eth-oxy-2,5-di-nitro-phen-yl)acetamide.
In the title compound, C10H11N3O6, the torsion angles about the bonds to the benzene ring are less than 4°, except for the nitro groups, which are twisted out of the ring plane by 25.27 (3) and 43.63 (2)°. The N-H group forms a bifurcated hydrogen bond, with an intra-molecular component to a nitro group O atom and an inter-molecular component to the other nitro group, thereby forming chains propagating in the [010] direction. Several weak C-H⋯O inter-actions are also present.


Risk Assessment and Prediction of Severe or Critical COVID-19 Illness in Older Adults.
This study is to investigate the risk prediction of severe or critical events of COVID-19 in older adults in China and provide the evidence to support the management of older adults with COVID-19. The clinical data of older adults with COVID-19 admitted to the Shanghai Public Health Clinical Center during January 20, 2020 to March 16, 2020 were collected. The possible risk factors of severe or critical illness were investigated with Cox proportional hazards (PH) regression models for univariate and multivariate analyses to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). For the prediction indicators, optimum cut-off points were determined by calculating Youden's index. The efficacy of risk prediction of severe or critical illness was examined through the receiver operating characteristic (ROC) curve. A total of 110 older adults with COVID-19 were included, in which 21 (19.1%) patients had severe or critical illness of COVID-19. Multivariable regression analysis showed that CD4 cells and D-dimer were independent risk factors. D-dimer, CD4 cells, and CD cells/D-dimer ratio with cut-off values of 0.65 (mg/L), 268 (cell/µL) and 431 were in the prediction of severe or critical illness of older adults with COVID-19. The AUC value of D-dimer, CD4 cells, CD4 cells/D-dimer ratio, the tandem combination and the parallel combination to predict severe or critical illness of the older adults with COVID-19 were 0.703, 0.804, 0.794, 0.812 and 0.694, respectively. D-dimer and CD4 cells either by themselves or in combination have demonstrated predictive value in risk stratification as well as established the prognosis of severe or critical illness in older adults with COVID-19.


No evidence for an association between glyoxalase I and haptoglobin in nine Spanish populations.
No association between glyoxalase I and haptoglobin phenotypes was found in 9 Spanish populations. This is in accordance with two out of three papers published.


Developmental effect of dimethyl sulfoxide on hypothalamo-neurohypophysial neurons in vitro.
Primary dissociated cultures were established from diencephalic tissue of 14-day-old fetal rats. Neurons exhibiting immunocytochemical staining for neurophysin appeared in these cultures after 6 days of cultivation. Addition of dimethyl sulfoxide (DMSO) to the culture medium resulted in a slight decrease in total neuronal cell mass as assessed by immunocytochemistry and radio-immunometric quantitation of neuron-specific enolase. In contrast, in DMSO-treated cultures the number of neurophysin-immunoreactive neurons was more than doubled as compared to control cultures. [3H]Thymidine labeling and autoradiography in conjunction with immunocytochemistry for neurophysin showed that this was not due to a mitogenic effect of DMSO on precursor cells. Time-course analysis of the action of DMSO revealed a 6-day time lag between the initiation of treatment and the appearance of increased numbers of neurophysin-immunoreactive cells. These findings suggest that DMSO, which has previously been reported to have a differentiation-inducing effect on malignant transformed cells, may also modulate cellular processes that control differentiation in specific types of neurons in primary culture.


The effect of discussing pain on patient-physician communication in a low-income, black, primary care patient population.
Patients and physicians report that discussions about pain are frequently frustrating and unproductive. However, the relationship between discussions about pain and patient-physician communication is poorly understood. We analyzed 133 video-recorded visits and patient self-report data collected at a clinic providing primary care to a low-income, black patient population. We used "thin slice" methods to rate two or three 30-second video segments from each visit on variables related to patient and physician affect (ie, displayed emotion) and patient-physician rapport. Discussions about pain were associated with a .32 increase in patient unease (P < .001) and a .21 increase in patient positive engagement (P = .004; standardized coefficients) compared to discussions about other topics during the same visit. Discussions about pain were not significantly associated with patient-physician rapport, physician unease, or physician positive engagement. Patient pain severity was significantly associated with greater physician and patient unease (P = .01), but not with other variables. Findings suggest that primary care patients, but not their physicians, display significantly greater emotional intensity during discussions about pain compared to discussions about other topics. This study used direct observation of video-recorded primary care visits to show that discussions about pain are associated with heightened displays of both positive and negative patient emotions. These displays of emotion could potentially influence pain-related outcomes.


Reducing hypertriglyceridemia in elderly patients with cerebrovascular disease stabilizes or improves cognition and cerebral perfusion.
Effects of lowering serum triglyceride levels were investigated among 44 elderly hypertriglyceridemic patients with risk factors for stroke, reduced cerebral perfusion, and a history compatible with symptomatic occlusive cerebrovascular disease. Patients were randomly assigned to either treatment with gemfibrozil, a lipid-lowering agent, or control conditions. Subjects in both groups were instructed to follow a diet recommended for lowering serum lipid levels, while the treatment group was additionally administered 600 mg daily of gemfibrozil. Subjects assigned to the treatment group (n = 22) showed significant reductions in serum triglyceride levels (p less than .0005). Control subjects (n = 22) did not show any significant changes in serum triglyceride levels. There were also no significant changes in total cholesterol levels in either group. Analyses of values for mean bihemispheric gray matter cerebral blood flow measured by the xenon 133 inhalation method and cognitive scores tested by the Cognitive Capacity Screening Examination indicated that gemfibrozil-treated patients maintained significantly higher levels of cerebral perfusion and cognitive performance than untreated controls did. Regression analyses for different treatment intervals indicated that both cerebral blood flow and cognition showed linear improvements that correlated directly with the duration of treatment. Lowering triglyceride levels in hyperlipidemic subjects appears to benefit cerebral perfusion and cognitive performance after four to six months.


Evaluation of apical extrusion of debris and centering ability in different nickel-titanium files during curved root canal preparation.
Curved root canals lead to difficulties in cleaning, shaping and filling the root canal system. Apical extrusion of debris and root canal transportation are important factors causing postoperative complications. In clinical practice, commonly selected instruments include multifile NiTi systems, such as M3-Pro PLUS (M3-PRO), Orodeka Plex 2.0 (ODP), Rotate (ROT), and Protaper Gold (PTG), as well as single-file NiTi systems, such as M3-L Platinum 2019 (M3L), Waveone Gold (WOG), and Reciproc Blue (RCB). This study aimed to comprehensively evaluate the differences in the apical extrusion of debris and centering ability of the above NiTi files. Seventy 3D-printed resin teeth were used (n = 10). The apically extruded debris was collected in a preweighed centrifuge tube. The resin teeth with or without root canal preparation were cut into separate cross sections at 1 mm, 3 mm, 5 mm, and 7 mm away from the root apex, and then the root canal transportation and centering ratio of each cross section were calculated. Apical extrusion of debris was highest in RCB but lowest in OD-P (P < 0.05). Root call deviation was lowest in ROT at the 3 mm level, in PTG at the 5 mm level, and in PTG and ROT at the 7 mm level (P < 0.05). The centering ratio of NiTi files was highest in the RCB group at the 3 mm level, in the PTG group at the 5 mm level, in the ROT group at the 7 mm level (P < 0.05). For NiTi files with the same system, the cross-sectional design is the greatest factor affecting the extrusion of debris, and motion mode is the second. In addition, the multifile system could reduce the degree of root canal transportation.


Amalgam restoration or just a deposit? A riveting incidental finding- a case report.
Parafunctional oral habits are known to cause deleterious effects on maxillofacial structures. One such effect is traumatic injuries secondary to chewing inanimate objects like pencils. Following trauma, the lead of the pencil has been reported to embed in the soft tissue of the oral cavity, appearing as a grayish pigmentation (graphite tattoo). However, such pigmentation has never been reported in the hard tissue (teeth). We hereby report an interesting, first of its kind case in a four-year-old female child. She had been misdiagnosed and referred for the management of a carious tooth; which was, in reality, an exogenous deposit. The authors highlight the impact of comprehensive history taking on arriving at the diagnosis. Counselling of the child and the parents goes a long way in flouting such deleterious habits.


K-ras mutations and benefit from cetuximab in advanced colorectal cancer.
Treatment with cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy. The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value. We analyzed tumor samples, obtained from 394 of 572 patients (68.9%) with colorectal cancer who were randomly assigned to receive cetuximab plus best supportive care or best supportive care alone, to look for activating mutations in exon 2 of the K-ras gene. We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups. Of the tumors evaluated for K-ras mutations, 42.3% had at least one mutation in exon 2 of the gene. The effectiveness of cetuximab was significantly associated with K-ras mutation status (P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival, respectively). In patients with wild-type K-ras tumors, treatment with cetuximab as compared with supportive care alone significantly improved overall survival (median, 9.5 vs. 4.8 months; hazard ratio for death, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001) and progression-free survival (median, 3.7 months vs. 1.9 months; hazard ratio for progression or death, 0.40; 95% CI, 0.30 to 0.54; P<0.001). Among patients with mutated K-ras tumors, there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival (hazard ratio, 0.98; P=0.89) or progression-free survival (hazard ratio, 0.99; P=0.96). In the group of patients receiving best supportive care alone, the mutation status of the K-ras gene was not significantly associated with overall survival (hazard ratio for death, 1.01; P=0.97). Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab. The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone. (ClinicalTrials.gov number, NCT00079066.)


Evaluation of the eradication program for Amblyomma variegatum (Acari:Ixodidae) on Puerto Rico.
A cooperative effort between the United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services, the Agricultural Research Service, and the Department of Agriculture, Commonwealth Government of Puerto Rico has been successful in eradicating Amblyomma variegatum (Fabricius) from the islands of Puerto Rico and Vieques (an island municipality of Puerto Rico). Application of acaricides to livestock and dogs at 14-day intervals for an 18-month period eliminated foci of tick infestation on 188 farms in four different locations without additional aerial or ground treatment. Reasons for the success and some of the costs associated with the eradication program on Puerto Rico are presented.


Cold-induced abortion in paramyotonia congenita.
Paramyotonia congenita is a rare autosomal dominant disorder with complete penetrance. Its most typical clinical feature is the precipitation of active myotonia by exposure to cold. We report a case of cold-induced abortion in a woman with paramyotonia congenita.


Anticancer and antimicrobial effects of novel ciprofloxacin fatty acids conjugates.
Ciprofloxacin (CP) has a confirmed cytotoxic action on some cancerous cells, but in high, non-pharmacological concentrations. Considering features of natural fatty acids, such as biocompatibility, biodegradability and their increased cellular uptake by cancer cells, it seems that combining them with a drug could improve its bioavailability, and thus cytotoxicity. Therefore, the aim of this study was coupling of CP with saturated and unsaturated fatty acids, and evaluation of their cytotoxicity, apoptosis-inducing effects and inhibition of IL-6 release in human primary (SW480) and metastatic (SW620) colon cancer, metastatic prostate cancer (PC3) and normal (HaCaT) cell lines. The PC3 cell line was the most sensitive to the presence of the obtained conjugates. The value of IC50 for oleic acid conjugate (4) was 7.7 μM, and it was 12 times lower than for CP alone (101.4 μM). The studied derivatives induced late apoptosis in all cancer cell lines, but not in normal cells. The most potent apoptosis inducer was conjugate 4, that resulted in the highest percentage of PC3 cells in late apoptosis (81.5% ± 3.9), followed by elaidic acid amide 5 (75% ± 4.8). The strongest pro-apoptic effects on SW480 cells were demonstrated by conjugates of DHA (8) and sorbic (2) acids, whereas in SW620 cell lines, compounds 2 and 5 appeared to be the most effective. To establish the mechanism of cytotoxic action of derivatives 2, 4, 5, the level of interleukin-6 (IL-6) was measured. The compounds with the highest cytotoxic potential significantly decreased the release of IL-6 by cancer cells. Additionally, all conjugates were evaluated for their in vitro antimicrobial activity. Short chain amides - crotonic (1) and sorbic (2) - were the most active against Staphyloccoci. The second-mentioned amide has shown both strong antistaphylococcal and antitumor properties.


Living in a network of scaling cities and finite resources.
Many urban phenomena exhibit remarkable regularity in the form of nonlinear scaling behaviors, but their implications on a system of networked cities has never been investigated. Such knowledge is crucial for our ability to harness the complexity of urban processes to further sustainability science. In this paper, we develop a dynamical modeling framework that embeds population-resource dynamics-a generalized Lotka-Volterra system with modifications to incorporate the urban scaling behaviors-in complex networks in which cities may be linked to the resources of other cities and people may migrate in pursuit of higher welfare. We find that isolated cities (i.e., no migration) are susceptible to collapse if they do not have access to adequate resources. Links to other cities may help cities that would otherwise collapse due to insufficient resources. The effects of inter-city links, however, can vary due to the interplay between the nonlinear scaling behaviors and network structure. The long-term population level of a city is, in many settings, largely a function of the city's access to resources over which the city has little or no competition. Nonetheless, careful investigation of dynamics is required to gain mechanistic understanding of a particular city-resource network because cities and resources may collapse and the scaling behaviors may influence the effects of inter-city links, thereby distorting what topological metrics really measure.


Heterangaeus Alexander, 1925 crane flies (Diptera: Pediciidae) of Korea.
The Korean crane fly species of the genus Heterangaeus Alexander, 1925 (Diptera: Pediciidae) is taxonomically revised. H. gloriosus gloriosus (Alexander, 1924) is redescribed. A new species Heterangaeus koreanus n. sp., which is the first species of Pediciidae from South Korea, is described and illustrated.


A qualitative and quantitative analysis of von Willebrand factor contained in a very high-purity plasma-derived FVIII concentrate.
We studied the structural and functional properties of von Willebrand factor (VWF) molecules present in a very high-purity plasma-derived factor VIII concentrate (VHP pdFVIII - Factane® ) because several observations suggest that the presence of VWF in factor VIII (FVIII) preparations may decrease their immunogenicity. Ten marketed batches of VHP pdFVIII (Factane® ) with levels of VWF ranging from 15 to 39 IU/100 IU FVIII were analysed. The VWF multimeric pattern was studied by agarose gel electrophoresis. The binding of VWF to FVIII was studied by gel filtration and ELISA. The binding of VWF to GPIb was analysed by ELISA. The results showed that high-molecular-weight multimers of VWF were present in VHP pdFVIII (Factane® ). VWF subunits maintain a triplet structure similar to that of normal plasma. Regardless of the VWF content, all FVIII molecules of each batch were co-eluted with VWF, and no free FVIII was detectable. By immunoassays, VWF was found to be able to bind to FVIII and platelet GPIb in a similar manner to that of VWF in normal plasma. In all the VHP pdFVIII (Factane® ) batches studied, regardless of the level of VWF, the structure and capacity of VWF binding to FVIII and to platelet GPIb were fully preserved.


Lymphocyte transformation test reveals low prevalence of true metal hypersensitivity among pre-operative total knee arthroplasty patients.
The aims of this study were to determine the prevalence of metal hypersensitivity, and identify pre-operative factors which could predict susceptibility to hypersensitivity reactions among patients scheduled for primary total knee arthroplasty (TKA). The present study used a testing method consistent with the recognised biological response to metals. A prospective cross-sectional analysis of 220 patients was conducted. All patients received a testing protocol using lymphocyte transformation test to evaluate reactivity to possible contents of orthopaedic implants. Test response is interpreted as stimulation index (SI) values. A comprehensive questionnaire was used to evaluate prior exposure. Patients were categorised according to SI values and the odds ratios (OR) were calculated as comparative effect measure for each predetermined prior exposure factor. The prevalence of metal sensitivity response was 28% (n = 61) among patients with susceptibility to at least one agent (SI = 2 to 4.9), and 3.2% (n = 7) among patients with true hypersensitivity (SI ≥ 5). The population-weighted prevalence, adjusted for sampling weights of symptomatic knee osteoarthritis, was SI ≥ 5 = 4.7% (95% CI 0.4-11.8%) and SI ≥ 2 = 35.2% (95% CI 24.8-48.6%). Stimulation index levels of response to materials were markedly varied with the highest being aluminium. Female sex, smoking history, cutaneous reaction to jewellery, occupational exposure, and dental procedures were among factors shown to increase the odds of having higher reactivity response to tested metals. Nevertheless, patients with well-functioning prior contralateral TKA did not appear at greater risk of having either sensitivity or susceptibility with odds ratio (OR) = 0.2 (95% CI 0.01-3.2), p: NS and OR = 0.6 (95% CI 0.3-1.2), p: NS, respectively. Prior positive patch test was neither predictor of susceptibility to hypersensitivity OR = 1.2 (95% CI 0.6-2.6) p: NS nor predictor of true hypersensitivity OR = 0.7 (95% CI 0.08-6.1), p: NS. Among patients scheduled for primary TKA with no prior clinical features of metal allergy the prevalence of true hypersensitivity to at least one metal is just over 3%. Patients are likely to encounter a material to which they have pre-existing susceptibility to hypersensitivity. With certain prior exposure factors, there was increased susceptibility to metal hypersensitivity reaction evoking an acquired condition. Level II, prospective cross-sectional study.


Valuing the European 'coastal blue carbon' storage benefit.
'Blue' carbon ecosystems are important carbon storage providers that are currently not protected by any international mechanism, such as REDD. This study aims to contribute to raising awareness in the political domain about the 'blue' carbon issue. This analysis also provides guidance in terms of how to value stock and flows of ecosystem services adding to the debate begun by the Costanza et al. (1997) paper in Nature. Through scenario analysis we assess how human welfare benefits will be affected by changes in the European coastal blue carbon stock provision. The current extent of European coastal blue carbon has an accounting stock value of about US$180 million. If EU Environmental Protection Directives continue to be implemented and effectively enforced, society will gain an appreciating asset over time. However, a future policy reversal resulting in extensive ecosystem loss could mean economic value losses as high as US$1 billion by 2060.


Emerging advances and current applications of nanoMOF-based membranes for water treatment.
Metal-organic frameworks (MOFs) are significantly tunable materials that can be exploited in a wide range of applications. In recent years, a large number of studies have been focused on synthesizing nano-scale MOFs (nanoMOFs), thus taking advantage of these unique materials in various applications, especially those that are only possible at nano-scale. One of the technologies where nanoMOF materials occupy a central role is the membrane technology as one of the most efficient separation techniques. Therefore, numerous reports can be found on the enhancement of the physicochemical properties of polymeric membranes by using nanoMOFs, leading to remarkably improved performance. One of the most considerable applications of these nanoMOF-based membranes is in water treatment systems, because freshwater scarcity is now an undeniable crisis facing humanity. In this in-depth review, the most prominent synthesis and post-synthesis methods for the fabrication of nanoMOFs are initially discussed. Afterwards, different nanoMOF-based composite membranes such as thin-film nanocomposites (TFN) and mixed-matrix membranes (MMM) and their various fabrication methods are reviewed and compared. Then, the impacts of using MOFs-based membranes for water purification through growing metal-organic frameworks crystals on the support materials and utilization of metal-organic frameworks as fillers in mixed matrix membrane (MMM) are highlighted. Finally, a summary of pros and cons of using nanoMOFs in membrane technology for water treatment purposes and clear future prospects and research potentials are presented.


Immune response mediated by liposome-associated protein antigens. III. Immunogenicity of bovine serum albumin covalently coupled to vesicle surface.
A protein antigen, bovine serum albumin (BSA), was covalently linked to the surface of preformed large unilamellar vesicles composed of phosphatidylcholine, cholesterol, and N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine (MPB-PE). The interaction between thiolated BSA and MPB-PE resulted in the production of a protein-liposome conjugate via the formation of an irreversible covalent bond. Mice immunized with liposome-coupled BSA were found to generate a vigorous BSA-specific plaque-forming cell (PFC) response. No significant response was observed in control animals given simultaneous, but separate injections of thiol-BSA and liposomes. Thus, there seems to be a need for successful and stable linkage between the antigen and the carrier. The elicitation of an optimal antigen-specific PFC response was also found to require the vesicle surface to be coated with a certain minimum distribution of the antigen. Results of this study demonstrate that the covalent coupling of a protein antigen to the liposome surface is very effective in potentiating the protein-specific antibody response and the immunogenicity of the conjugate is dependent on the epitope density of the antigen.


Case of an abnormal procalcitonin-producing metastatic pancreatic neuroendocrine tumor.
Procalcitonin (PCT) is widely used to diagnose a bacterial infection. An increased serum PCT can also be observed in tumors. We presented an unusual case of a metastatic PNET producing and secreting PCT. Immunohistochemistry was used to demonstrate that PCT can be secreted by PanNET.


Tumor homologous recombination deficiency assays: another step closer to clinical application?
Inherited and acquired defects in homologous recombination, a phenotype termed 'BRCAness', may lend to therapeutic exploitation in breast cancer. To this end, development and clinical evaluation of platforms to identify signatures of BRCAness are of immense interest. In this issue of Breast Cancer Research, Vollebergh and colleagues report that a BRCA-like array comparative genomic hybridization (aCGH) genomic instability signature is associated with benefit from high-dose cyclophosphamide-thiotepa-carboplatin chemotherapy. We discuss the strengths and weaknesses of this study and consider the clinical significance and applicability of this aCGH BRCAness signature in the context of other existing homologous recombination deficiency detection platforms.


A binary module for microbiota-mediated regulation of γδ17 cells, hallmarked by microbiota-driven expression of programmed cell death protein 1.
Little is known about how microbiota regulate innate-like γδ T cells or how these restrict their effector functions within mucosal barriers, where microbiota provide chronic stimulation. Here, we show that microbiota-mediated regulation of γδ17 cells is binary, where microbiota instruct in situ interleukin-17 (IL-17) production and concomitant expression of the inhibitory receptor programmed cell death protein 1 (PD-1). Microbiota-driven expression of PD-1 and IL-17 and preferential adoption of a PD-1high phenotype are conserved for γδ17 cells across multiple mucosal barriers. Importantly, microbiota-driven PD-1 inhibits in situ IL-17 production by mucosa-resident γδ17 effectors, linking microbiota to their simultaneous activation and suppression. We further show the dynamic nature of this microbiota-driven module and define an inflammation-associated activation state for γδ17 cells marked by augmented PD-1, IL-17, and lipid uptake, thus linking the microbiota to dynamic subset-specific activation and metabolic remodeling to support γδ17 effector functions in a microbiota-dense tissue environment.


Reduction of sulfide, ammonia compounds, and adhesion properties of Lactobacillus casei strain KE99 in vitro.
The ability of Lactobacillus casei strain KE99 to reduce sulfide, ammonia, and to adhere to bio-surfaces was characterized and compared with three lactobacillus reference strains. Sulfide reduction by strain KE99 in MRS broth increased exponentially after 10-h growth and reached a maximum (>300 ppm reduction) within 48 h. KE99 demonstrated a maximum reduction of sulfide under anaerobic (341 ppm) growth conditions at pH 6.0-8.0 range. Maximum anaerobic reduction of sulfide was demonstrated by L. casei 393 at pH 7.0 (272 ppm); L. rhamnosus at pH 8.0 (277 ppm); and L. reuteri at pH 7.0 (244 ppm). KE99 reduced sulfide more (p < 0.0001) in MRS broth spiked with Na2S (374 ppm) than (NH4)2S (340 ppm) salts. Ammonia reduction by strain KE99 and the three lactobacillus reference strains in MRS broth was low. Ammonia reduction reached a maximum within 36 h and remained unchanged over extended incubations of 48 h to 72 h or further. KE99 reduced ammonium sulfate (37 ppm) more readily than the nitrate (31 ppm), hypophosphate (29 ppm), or chloride (20 ppm) salts of ammonia. KE99 and the three reference strains of lactobacilli demonstrated avid binding to Bio-coat (Cn type-I, Cn type-IV, laminin, fibronectin), Matrigel, and Caco-2 cell monolayers in vitro. The number of lactobacilli binding to Caco-2 was estimated at 74/cell with strain KE99, which was significantly higher compared with 40/cell (p < 0.0001), 26/cell (0.0001), and 64/cell (p < 0.002) with L. casei 393, L. reuteri, and L. rhamnosus, respectively. The interaction of KE99 to immobilized Cn type-I was saturable and reached an equilibrium within 1 h at room temperature. KE99 binding to Cn type-I occurred at a wide pH range and was biphasic with maximum binding at pH 5.5 and 7.5. Inhibition and binding-displacement experiments with different salts and sugars suggested that the KE99 binding to immobilized Cn type-I may involve a combination of electrostatic and lectin-type interactions. KE99 effectively detached the Cn-adherent E. coli O157:H7 in the range of 55% (ATCC43895) to 76% (ATCC43894). The binding-displacement values for L. casei 393, L. reuteri and L. rhamnosus to detach Cn-adherent E. coli O157:H7 (ATCC43894) were 66 +/- 4%, 59 +/- 2%, and 64 +/- 2%, respectively. Also, a reconstituted solution of the freeze-dried KE99 preparation effectively detached the Cn-adherent E. coli O157:H7 in a dose-dependent manner that reached a binding-displacement equilibrium of 85% at a 1% wt/vol KE99 concentration.


Lymphocyte-suppressing action of simvastatin in patients with isolated hypertriglyceridemia.
No previous study examined whether statins affect lymphocyte cytokine release in patients with isolated hypertriglyceridemia. The study included 46 patients with elevated triglyceride levels and peripheral artery stenosis, randomly assigned to receive simvastatin or placebo. Plasma lipids, glucose homeostasis markers, plasma C-reactive protein and lymphocyte cytokine release were measured at baseline and at the end of the treatment. Ninety-day simvastatin treatment reduced lymphocyte release of TNF-α, interleukin-2 and interferon-γ, which was accompanied by a decrease in plasma C-reactive protein. The obtained results suggest that statins produce lymphocyte-suppressing and systemic anti-inflammatory effects in patients with isolated hypertriglyceridemia.


Adaptations of peripheral vasoconstrictor pathways after spinal cord injury.
The consequences of spinal cord injury on the function of sympathetic pathways in the periphery have generally been ignored. We discuss two types of plasticity that follow disruption of sympathetic pathways in rats . The first relates to the partial denervation of sympathetic ganglia that would follow the loss of some preganglionic neurones. Sprouting of residual connections rapidly reinnervates many postganglionic neurones, restoring functional transmission within a few weeks, but other neurones may be permanently decentralized. Some of the new functional connections may generate inappropriate pathways leading to abnormal reflexes . The second type of plasticity concerns the markedly enhanced and prolonged contractile responses to nerve activity in arterial vessels to which ongoing sympathetic activity has been reduced or silenced following spinal cord transection or ganglion decentralization. In a cutaneous artery (the rat tail artery), the mechanisms underlying this arterial hyperreactivity differ from those in the splanchnic arteries (the rat mesenteric artery). In the former, hyperreactivity is mainly postjunctional but independent of changes in alpha1-adrenoceptor sensitivity, whereas the increased responsiveness in the latter vessels can be attributed to a greater responsiveness to alpha1-adrenoceptor activation. There are enough data from humans to suggest that both of these novel findings in experimental animals are likely to apply after spinal cord injury and contribute to autonomic dysreflexia .


African Federation for Emergency Medicine's Francophone Working Group - May 2018 Report.
Even though the African Federation for Emergency Medicine (AFEM) has been successfully developing emergency care in Africa for the past nine years, a considerable amount of potential AFEM members from the African-Francophone countries are not able to access AFEM resources. In response, an AFEM Francophone Working Group has been created to coordinate all existing and new initiatives to promote emergency care in African-Francophone countries.


Microlearning through the Lens of Gagne's Nine Events of Instruction: A Qualitative Study.
Microlearning provides a valuable and efficient strategy for delivering content to students. As online enrollments continue to increase, further research is needed to determine how students experience microlearning in an online learning format. In this qualitative study, a focus group was used to explore how learners experienced an online microlearning activity through the lens of Robert Gagné's nine events of instruction. Gagné's framework is designed to maximize cognitive processing and learner engagement. Using a hybrid process of deductive and inductive thematic analysis, learners' experiences were used to determine if each of Gagné's nine events were present during a selected online microlearning activity. This study revealed that eight of Gagné's nine events were detected. The results provide faculty with a better understanding of how students experience online microlearning and will inform faculty and course designers of critical elements to consider in the development of future online microlearning instruction.


Association between polymorphisms in the interleukin-10 gene and susceptibility to human immunodeficiency virus-1 infection: A systematic review and meta-analysis.
This study meta-analyzed the literature on possible association of 3 polymorphisms (-592, -1082, -819) in the interleukin-10 (IL-10) gene with susceptibility to human immunodeficiency virus (HIV)-1 infection. PubMed, EMBASE, MEDLINE and Google Scholar were systematically searched to identify relevant studies in English. Meta-analyses were performed to examine the association of IL-10 polymorphisms -592, -1082, and -819 with susceptibility to HIV-1 infection. A significant association between the -592 polymorphism and susceptibility to HIV-1 infection was found in the total population (recessive model, odds ratios (OR) = 1.44, 95% CI = 1.06-1.96, P = .02; homozygous model, OR = 1.44, 95% CI = 1.02-2.02, P = .04). However, these results were not observed in subgroups based on ethnicity. The -1082 polymorphism was significantly associated with susceptibility to HIV-1 infection in Caucasians (OR = 1.30, 95% CI = 1.05-1.62, P = .02; recessive model, OR = 1.49, 95% CI = 1.09-2.03, P = .01; homozygous model, OR = 1.58, 95% CI = 1.01-2.46, P = .04), but not in Asians or the total population. None of the 5 genetic models suggested a significant association between the -819 polymorphism and HIV-1 infection. The available evidence indicates that the AA genotype of IL-10 -592 may confer increased susceptibility to HIV-1 infection, and that the AA genotype of -1082 may confer increased susceptibility in Caucasians. In contrast, the -819 polymorphism may not be associated with HIV-1 infection risk. These conclusions should be verified in large, well-designed studies.


Chronic metformin intake and gastric cancer: A pooled analysis within the Stomach cancer Pooling (StoP) Project.
The association between chronic use of metformin and risk of gastric cancer (GC) has been investigated with contradicting results. We aimed to study the association between chronic use of metformin and GC by using data from the Stomach cancer Pooling (StoP) Project, an epidemiological consortium of case-control studies on GC. Data from three studies of the StoP Project with available information on metformin intake were analyzed. Multivariable logistic regression models were used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between chronic use of metformin and GC risk. Analyses were adjusted for sex, age, socioeconomic status, body mass index, smoking status, alcohol drinking status, and history of diabetes. Study-specific ORs and 95% CIs were then pooled with a random-effects model. The dose-response relationship between the duration of metformin intake and GC was assessed with a one-stage logistic model, and the duration of intake was modelled using second-order fractional polynomials. The OR of GC in metformin users versus non-users was 1.01 (95% CI=0.61, 1.67). The association between metformin and GC did not change among different strata of study participants' characteristics or when restricting the analyses to those with a history of diabetes. The dose-response analysis showed a slightly reducing trend in the OR of GC and a borderline significant association with increasing duration of metformin intake. The results of our study do not clearly support an association between chronic use of metformin and GC, warranting further research.


Helicopter rescue and prehospital care for drowning children: two summer season case studies.
Drowning is the second leading cause of unintentional injury-related death in children <14 years of age and is one of the most important causes of accidental injury between the ages of 1 and 4 years. In this study, the characteristics of non-fatal unintentional drownings in a small series of pediatric victims were examined. We retrospectively analyzed data collected by the rescue team from May to October in two consecutive years (2006, 2007). Nine accidents occurred in public waters, while 5 occurred in lakes and rivers. The submersion time reported ranged from approximately 5 to 15 min. The ground emergency service with basic life support rescue experts intervened within a mean of 12 min. Advanced cardiac life support maneuvers were implemented by the helicopter medical crew for all victims. Ten of the 14 children remained in cardiocirculatory arrest despite cardiopulmonary resuscitation (CPR). The Glasgow Coma Scale (GCS) was <8 in all cases. Field resuscitation ultimately proved successful for every child. Thus, none was transported by the helicopter with ongoing CPR. All submersion-injured children survived. No postanoxic cerebral injury or major neurological complications were detected. Assuring safe tracheal ventilation, achieving intravenous access, and stabilizing both respiratory and hemodynamic disturbances on the ground before transferring the patient are the keys to out-of-hospital management. Our 100% survival rate likely results from adequate primary out of-hospital care. Promptly dispatching a helicopter with a specialized medical crew is very expensive, but is worth the cost because it offers a better chance of survival.


Protein labeling and biotinylation of peptides during spot synthesis using biotin p-nitrophenyl ester (biotin-ONp).
Biotin-labeled peptides are used for numerous biochemical and microbiological applications. Due to the strong affinity of biotin to streptavidin, the detection of biotinylated molecules is very sensitive. A powerful technique for parallel synthesis and high-throughput screening of peptides is the spot synthesis. One example for the use of spot synthesis is the screening of biotinylated peptides synthesized on cellulose membranes, which is particularly favorable for the investigation of protease cleavage sites. Additionally, in combination with biotinylated protein samples, the spot technique can be used for investigations of peptide-protein and protein-protein interactions. Here, we present our results of the use biotin p-nitrophenyl ester (biotin-ONp) in spot synthesis and as a reagent for biotin-labeling of protein samples.


Development of a time-resolved fluorescence immunoassay based on immunomagnetic beads for gastrin-17.
In this study, a novel, simple, and rapid immunoassay for the determination of gastrin-17 (G-17) in human serum was established by combining immunomagnetic beads with time-resolved fluorescence immunoassay (TRFIA). Immunomagnetic beads were coated with anti-G-17 M01 antibody, anti-G-17 M02 antibody was labeled with Eu3+ chelates. The concentration of G-17 in the serum was detected with the double-antibody sandwich method. The limit of background(LOB), limit of detection (LOD), and limit of quantification (LOQ) were 0.09, 0.104, and 0.39 pmol/L, respectively. The detection range of G-17-TRFIA was 0.39-100 pmol/L. The average intra- and inter-assay coefficients of variation (CV) were 5.95%-9.07% and 6.09%-8.14%, respectively. The recoveries for the serum samples ranged from 94.70% to 100.95%. The specificity of our G-17-TRFIA was acceptable. The correlation coefficient between G-17-TRFIA and commercial G-17-ELISA methods was R2 = 0.9092. A novel G-17-TRFIA detection method was successfully established to provide a reference for the early diagnosis of patients with atrophic gastritis in clinical research.


Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection.
Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a host factor for Zika virus (ZIKV) infection. In this study, we extended our analysis to trophectoderm cells, which constitute one of the major routes of mother-to-fetus transmission of ZIKV during pregnancy. We differentiated hiPSCs from various donors into trophectoderm cells. We then infected cells carrying loss of function mutations in NDUFA4, harboring risk versus non-risk alleles of SNPs (rs917172 and rs12386620) or having deletions in the NDUFA4 cis-regulatory region with ZIKV. We found that loss/reduction of NDUFA4 suppressed ZIKV infection in trophectoderm cells. This study validated our published hiPSC array-based system as a useful platform for GWAS and confirmed the role of NDUFA4 as a susceptibility locus for ZIKV in disease-relevant trophectoderm cells.


The effects of febuxostat on the pharmacokinetic parameters of rosiglitazone, a CYP2C8 substrate.
To determine the effect of febuxostat on cytochrome P450 2C8 (CYP2C8) activity using rosiglitazone as a CYP2C8 substrate. Healthy subjects received febuxostat 120 mg daily (regimen A) or matching placebo (regimen B) for 9 days along with a single oral dose of rosiglitazone 4 mg on day 5 in a double-blind, randomized, cross-over fashion (≥7 day washout between periods). Plasma samples for analysis of the impact of febuxostat on the pharmacokinetics (PK) of rosiglitazone and its metabolite, N-desmethylrosiglitazone, were collected for 120 h after co-administration. Of the 39 subjects enrolled, 36 completed the study and were included in the PK analyses. Rosiglitazone PK parameters were comparable between regimens A and B. Median time to maximal plasma concentration, mean maximal plasma concentration (C(max)), area under the concentration-time curve (AUC) from time zero to the last quantifiable concentration (AUC(0-tlqc)), AUC from time zero to infinity (AUC(0-∞)), and terminal elimination half-life for regimen A were 0.50 h, 308.6 ng ml⁻¹, 1594.9 ng h ml⁻¹, 1616.0 ng h ml⁻¹ and 4.1 h, respectively, and for regimen B they were 0.50 h, 327.6 ng ml⁻¹, 1564.5 ng h ml⁻¹, 1584.2 ng h ml⁻¹ and 4.0 h, respectively. Point estimates for the ratio of regimen A to regimen B (90% confidence intervals) for rosiglitazone C(max) , AUC(0-tlqc) and AUC(0-∞) central values were 0.94 (0.89-1.00), 1.02 (1.00-1.04) and 1.02 (1.00-1.04), respectively. Co-administration of febuxostat had no effect on rosiglitazone or N-desmethylrosiglitazone PK parameters, suggesting that febuxostat can be given safely with drugs metabolized through CYP2C8.


Comparison of the Drosophila melanogaster, human and murine Sm B cDNAs: evolutionary conservation.
To analyze the evolutionary stability of the Sm B polypeptides, the cDNA nucleotide (nt) sequence was derived for the Drosophila melanogaster Sm B polypeptide and compared to the cDNAs encoding human and murine Sm B. The three cDNAs were transcribed and translated in reticulocyte lysates followed by analysis of the synthesized proteins by SDS-PAGE. D. melanogaster B migrated at approximately 25 kDa, in comparison to 28 kDa for the murine and human B proteins, although all three proteins were immunoprecipitated by human anti-Sm autoantibodies and by the Y12 anti-Sm murine monoclonal antibody (Y12 mAb). Immunoblots and immunoprecipitations of [35S]methionine-labeled D. melanogaster S2/M3 cells confirmed the smaller size of the D. melanogaster protein, and revealed that B' was absent in this cell line, as in murine cells. In comparison to the 231 amino acids (aa) of human and murine B, the deduced sequence for the D. melanogaster clone was 199 aa (predicted M(r) of 24,598) with two 5-aa deletions and a 19-aa truncation at the 3' end, compared to the other two clones. D. melanogaster protein B shared 65% aa sequence identity with the human and mouse clones, and 80% similarity when conservative aa substitutions were noted. The C-terminal portion of the D. melanogaster protein was the most evolutionarily variable in comparison to the deduced aa sequences for the other two proteins; however, autoantigenic epitopes bound by human anti-Sm antibodies and the Y12 mAb in this region of the protein were conserved across species lines.(ABSTRACT TRUNCATED AT 250 WORDS)


BRCA1 partially reverses the transforming activity of the ras oncogene.
The BRCA1 gene is associated with hereditary breast and ovarian cancers. BRCA1 fits the model of a classic tumor suppressor gene, a hypothesis supported by recent work demonstrating that expression of BRCA1 inhibits growth of breast and ovarian cancer cell lines. The present study was designed to test the potential of BRCA1 to reverse the transforming activity of the ras oncogene. The v-Ha ras oncogene was cloned downstream of the retrovirus LTR and stably expressed in Rat-1 cells (Rat-1/ras). Rat-1/ras (R/R) cells were fully transformed as indicated by change in morphology, colony formation in soft-agarose and tumor induction in nude mice. BRCA1 was stably expressed in R/R cells under the CMV promoter (R/R-BRCA1). The expression of ras and BRCA1 was confirmed by Western blot using monoclonal antibodies (mAbs) specific to ras and BRCA1, respectively. R/R-BRCA1 cells grew slower than the negative control, which was R/R cells transfected with vector alone (R/R-pCEP4). R/R-BRCA1 cells generated approximately 5 to 10 times less colonies in a soft-agarose assay compared to the negative control. When injected into nude mice, R/R-BRCA1 cells exhibited a delayed onset of tumorigenesis and generated smaller tumors compared to R/R or R/R-pCEP4 cells. These data strongly suggest that BRCA1 partially reverses the transforming activity of the v-Ha ras oncogene indicating that BRCA1 can bypass the effects of the v-Ha ras oncogene on cell growth. BRCA1, therefore, may be used in therapy of tumors arising due to activation of v-Ha ras oncogene.


[Biosynthesis of nicotinamide dinucleotide (NAD) in microorganisms (review of the literature)].
Data on the biosynthesis of nicotinamide adenine dinucleotide (NAD) and mechanisms of its regulation in microorganisms are reviewed, and the reasons and conditions of NAD overproduction are discussed.


Genome sequence analysis provides insights into the mode of 2n egg formation in Solanum malmeanum.
Our genomic investigation confirms the mechanism of 2n eggs formation in S. malmeanum and aid in optimizing the use of wild germplasm. Wild potatoes are a valuable source of agronomic traits. However, substantial reproductive barriers limit gene flow into cultivated species. 2n gametes are instrumental in preventing endosperm abortion caused by genetic imbalances in the endosperm. However, little is known about the molecular mechanisms underlying the formation of 2n gametes. Here, the wild species Solanum malmeanum Bitter (2x, 1EBN, endosperm balance number) was used in inter- and intrapoloid crosses with other Solanum species, with viable seeds being produced only when S. malmeanum was used as the female parent to cross the 2EBN Solanum genus and with the likely involvement of 2n gametes. Subsequently, we substantiated the formation of 2n eggs in S. malmeanum using fluorescence in situ hybridization (FISH) and genomic sequencing technology. Additionally, the transmission rate of maternal heterozygous polymorphism sites was assessed from a genomic perspective to analyze the mode of 2n egg formation in S. malmeanum × S. tuberosum and S. malmeanum × S. chacoense crosses; each cross acquired an average of 31.12% and 22.79% maternal sites, respectively. This confirmed that 2n egg formation in S. malmeanum attributed to second-division restitution (SDR) coupled with the occurrence of exchange events. The high-throughput sequencing technology used in this study has strong advantages over traditional cytological analyses. Furthermore, S. malmeanum, which has a variety of excellent traits not available from present cultivated potato genepool, has received little research attention and has successfully achieved gene flow in cultivated species in the current study. These findings will facilitate the understanding and optimization of wild germplasm utilization in potatoes.


[Prevention of thromboembolism with antiaggregants (author's transl)].
Experimental investigations have shown that antiaggregants affect the size rather than the rate of venous thrombosis, while clinical trials with prophylactic acetylsalicylic acid have indicated primarily a reduced incidence of pulmonary embolism. Current experiences with acetylsalicylic acid in combination with dipyridamole or low-dose heparin suggest that the incidence of pathology diagnosed by 125I-fibrinogen and of deep vein thrombosis is equally reduced.


The association of suicide attempts and comorbid depression and substance abuse in psychiatric consultation patients.
Substance abuse has been associated with attempted suicide and suicide. Few studies have examined the prevalence and associations of combined depression and substance abuse in suicide attempters. A chart review study of 1136 adult general hospital patients referred for psychiatric consultation between 1995 and 1998 was conducted to assess this further. Among 371 cases with self-harm, 311 (84%) attempted suicide. Suicide attempters were younger and diagnosed more often with comorbid substance abuse than patients without self-harm. Depressive disorders were found in 59% and substance abuse disorders in 46%. Comorbid depression and substance abuse was the most frequent category in suicide attempters, i.e., in 37%. Self-reported suicide intent was associated with increasing age, male gender, and comorbid depression and substance abuse. The suicide rate in suicide attempters was 322 per 100,000 patient-years, and 131 per 100,000 in consultation patients without self-harm. It is concluded that comorbid depression and substance abuse is associated with attempted suicide in psychiatric consultation patients. Suicide attempters should be thoroughly assessed for substance abuse. The increased suicide rate in psychiatric consultation patients with and without suicide attempts warrants further research.


[Iliopsoas impingement after cementless total hip arthroplasty. Case reports].
Postoperative pain after total hip arthroplasty can be caused by several conditions. We describe two cases of postoperative persistent iliopsoas impingement after cementless implantation of the acetabular component. The groin pain was relieved after revision with a more anteverted acetabular component. We describe the diagnostic methods as well as the principles of the revision.


ANGUSTIFOLIA3 signaling coordinates proliferation between clonally distinct cells in leaves.
Coordinated proliferation between clonally distinct cells via inter-cell-layer signaling largely determines the size and shape of plant organs. Nonetheless, the signaling mechanism underlying this coordination in leaves remains elusive because of a lack of understanding of the signaling molecule (or molecules) involved. ANGUSTIFOLIA3 (AN3, also called GRF-INTERACTING FACTOR1) encodes a putative transcriptional coactivator with homology to human synovial sarcoma translocation protein. AN3 transcripts accumulate in mesophyll cells but are not detectable in leaf epidermal cells. However, we found here that in addition to mesophyll cells, epidermal cells of an3 leaves show defective proliferation. This spatial difference between the accumulation pattern of AN3 transcripts and an3 leaf phenotype is explained by AN3 protein movement across cell layers. AN3 moves into epidermal cells after being synthesized within mesophyll cells and helps control epidermal cell proliferation. Interference with AN3 movement results in abnormal leaf size and shape, indicating that AN3 signaling is indispensable for normal leaf development. AN3 movement does not require type II chaperonin activity, which is needed for movement of some mobile proteins. Taking these findings together, we present a novel model emphasizing the role of mesophyll cells as a signaling source coordinating proliferation between clonally independent leaf cells.


Multisensory stimulation decreases phantom limb distortions and is optimally integrated.
The multisensory integration of signals from different senses is crucial to develop an unambiguous percept of the environment and our body. Losing a limb causes drastic changes in the body, sometimes causing pain and distorted phantom limb perception. Despite the debate over why these phenomena arise, some researchers suggested that they might be linked to an impairment of multisensory signals inflow and integration. Therefore, reestablishing optimally integrated sensory feedback could be crucial. The related benefits on sensory performance and body self-representation are still to be demonstrated, particularly in lower-limb amputees. We present a multisensory framework combining Virtual reality and electro-cutaneous stimulation that allows the optimal integration of visuo-tactile stimuli in lower-limb amputees even if nonspatially matching. We also showed that this multisensory stimulation allowed faster sensory processing, higher embodiment, and reductions in phantom limb distortions. Our findings support the development of multisensory rehabilitation approaches, restoring a correct body representation.


A forged 'chimera' including the second specimen of the protostegid sea turtle Santanachelysgaffneyi and shell parts of the pleurodire Araripemys from the Lower Cretaceous Santana Group of Brazil.
Fossils of Cretaceous sea turtles adapted to an open marine lifestyle remain rare finds to date. Furthermore, the relationships between extant sea turtles, chelonioids, and other Mesozoic marine turtles are still contested, with one key species being Santanachelys gaffneyi Hirayama, 1998, long considered the earliest true sea turtle. The species is an Early Cretaceous member of Protostegidae, a controversial clade either placed within or closely related to Chelonioidea or, alternatively, along the stem lineage of hidden-neck turtles (Cryptodira) and representing an independent open marine radiation. Santanachelys gaffneyi is one of the most completely preserved early protostegids and is therefore critical for establishing the global phylogenetic position of the group. However, the single known specimen of this taxon is yet to be described in detail. Here we describe a second specimen of Santanachelys gaffneyi from its type horizon, the Romualdo Formation (late Aptian) of the Santana Group of the Araripe basin, NE Brazil. The skeletal elements preserved include the posterior part of the skull, neck vertebrae, shoulder girdle, anterior-most and left/central part of the carapace with few peripherals, and plastron lacking most of the hyoplastra. The remaining part of the carapace was apparently completed by fossil dealers using an anterior part of the pleurodiran Araripemydidae, tentatively identified as a shell portion of cf. Araripemys barretoi, a more common Santana fossil turtle, among other indeterminate turtle shell fragments. The purpose of this paper is to report the repatriation of the specimen to Brazil and to provide a preliminary description. The online version contains supplementary material available at 10.1186/s13358-023-00271-9.


Sarcocystis Species Richness in Sheep and Goats from Lithuania.
Contradictory data is available on the intermediate host specificity of Sarcocystis spp. in farm animals. Therefore, the current work aimed at molecularly testing samples of sheep and goats reared in Lithuania to identify Sarcocystis species described in other intermediate hosts but suspected to be non-canonical parasites to these small ruminants. For this purpose, muscle samples from 47 domestic sheep and nine goats were examined. Sarcocystis species were identified using direct and nested PCR targeting cox1 and sequencing of positive amplified products. Along with the detection of the canonical Sarcocystis spp. in their respective intermediate hosts, the DNA of S. capracanis and S. morae was detected in sheep, although these species were previously thought to be specific to goats and deer, respectively. In addition, DNA from S. arieticanis and S. tenella was found in goats, even though these two species were believed to be sheep-specific. Notably, under light microscopy, only sarcocysts of S. capracanis specific to goats were observed. Thus, future research on the life cycle and host-specificity of Sarcocystis spp. examined is warranted.


Tailored Poly(vinylidene fluoride-co-trifluoroethylene) Crystal Orientation for a Triboelectric Nanogenerator through Epitaxial Growth on a Chitin Nanofiber Film.
Tailoring the crystal orientation of poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) has attracted widespread interest because of its effects on the ferroelectric properties required for various electronic devices. In this study, we investigated the epitaxial growth of PVDF-TrFE on a chitin film for developing triboelectric nanogenerators (TENGs). The crystallographic match between the chitin and PVDF-TrFE enables the development of the intended crystal orientation, with the PVDF-TrFE polarization axis aligned perpendicular to the substrate. In addition, the epitaxially grown PVDF-TrFE on chitin not only enhances the performance of the TENG but also increases the stability of the hygroscopic chitin film against water. The corresponding TENG exhibits a significantly higher output current compared to that of a nonepitaxial PVDF-TrFE/chitin film. Furthermore, the triboelectric sensors based on epitaxial PVDF-TrFE/chitin films allow the monitoring of subtle pressures, suggesting that tailoring the crystal orientation of PVDF-TrFE is a promising approach for developing high-performance TENGs.


Calcium absorption in the rat colon measured in vivo.
Calcium absorption in the large intestine was studied under physiological conditions in the rat. When 45Ca was administered directly into the caecum, the isotope was significantly absorbed. This absorption was modulated by dietary Ca and Pi as well as by the 1,25(OH) D3 status. On the other hand, calcium coming from the food, either as 45Ca or as 40Ca, was not absorbed to a significant amount. When the absorption of 45Ca from the caecal content was assessed in duodenal loops, less 45Ca was absorbed when the isotope was administered orally than when it was added to the caecal content. Thus, the fact that oral Ca is not absorbed in the colon despite the efficient Ca transport system of this part of the intestine may be due to the transformation in the digestive tract of Ca from an absorbable into a non-absorbable form.


Importance of mediastinal screening-based observation during endoscopic ultrasound to examine gastrointestinal pathologies.
In all endoscopic ultrasound (EUS) examinations performed at our hospital, the heart, vasculature, and mediastinal lymph nodes from the esophagus are observed after checking for gastrointestinal pathologies. Since the introduction of EUS using a convex linear-array echoendoscope at our hospital in April 2015, EUS examinations have been performed in 371 cases for examining pancreaticobiliary diseases, submucosal tumors, and other pathologies during the 3-year period, till March 2018. We diagnosed 2 patients with asymptomatic cardiovascular disease while observing the mediastinum during EUS examination to examine identified pancreaticobiliary disease. No subjective symptoms associated with cardiovascular disease were observed and the respective conditions had not been identified previously in either case. One case involved a left atrial myxoma while the other involved a saccular aortic aneurysm in the thoracic aorta. A left atrial tumor resection and aortic replacement surgery were performed in each case. Their postoperative courses have been favorable. As cardiovascular diseases are often life-threatening, as in the present 2 cases, observational screening of the cardiovascular system from the esophagus should also be performed during EUS examinations just as the pharyngeal region is examined during upper gastrointestinal endoscopy.


IL-33's role in the gut immune system: A comprehensive review of its crosstalk and regulation.
The intestinal tract is the largest immune organ in the human body, comprising a complex network of immune cells and epithelial cells that perform a variety of functions such as nutrient absorption, digestion, and waste excretion. Maintenance of homeostasis and effective responses to injury in the colonic epithelium are crucial for maintaining homeostasis between these two cell types. The onset and perpetuation of gut inflammation, characterizing inflammatory bowel diseases (IBD), are triggered by constitutive dysregulation of cytokine production. IL-33 is a newly characterized cytokine that has emerged as a critical modulator of inflammatory disorders. IL-33 is constitutively expressed in the nuclei of different cell types such as endothelial, epithelial, and fibroblast-like cells. Upon tissue damage or pathogen encounter, IL-33 is released as an alarmin and signals through a heterodimer receptor that consists of serum Stimulation-2 (ST2) and IL-1 receptor accessory protein (IL-1RAcP). IL-33 has the ability to induce Th2 cytokine production and enhance both Th1 and Th2, as well as Th17 immune responses. Exogenous administration of IL-33 in mice caused pathological changes in most mucosal tissues such as the lung and the gastrointestinal (GI) tract associated with increased production of type 2 cytokines and chemokines. In vivo and in vitro, primary studies have exhibited that IL-33 can activate Th2 cells, mast cells, or basophils to produce type 2 cytokines such as IL-4, IL-5, and IL-13. Moreover, several novel cell populations, collectively referred to as "type 2 innate lymphoid cells" were identified as being IL-33 responsive and are thought to be important for initiating type 2 immunity. Nevertheless, the underlying mechanisms by which IL-33 promotes type 2 immunity in the GI tract remain to be fully understood. Recently, it has been discovered that IL-33 plays important roles in regulatory immune responses. Highly suppressive ST2 + FoxP3+ Tregs subsets regulated by IL-33 were identified in several tissues, including lymphoid organs, gut, lung, and adipose tissues. This review aims to comprehensively summarize the current knowledge on IL-33's role in the gut immune system, its crosstalk, and regulation. The article will provide insights into the potential applications of IL-33-based therapies in the treatment of gut inflammatory disorders.


Multi-omics analyses reveal relationships among polyphenol-rich oolong tea consumption, gut microbiota, and metabolic profile: A pilot study.
Convincing evidence has suggested the health potentials of oolong tea (OT) on gut microbiota homeostasis; however, limited population-based studies exist regarding the effect of OT consumption on human gut microbial and metabolic profile. This pilot study explored gut microbial and metabolic changes in healthy adults with a 3-week oolong tea intake. Our findings showed that OT treatment significantly altered gut microbial diversity (Shannon index, 5.4±0.1 vs. 5.7±0.1 pre- and post-OT treatment), reorganized gut microbiota composition, enriched Bacteroides and Prevotella, decreased Megamonas, and improved gastrointestinal function. Also, gut microbes from overweight subjects with BMI >23.9 exhibited greater responses to OT treatment compared with normal-weight counterparts. Metabolomic analysis identified OT intake-induced 23 differential metabolites and 10 enriched metabolic pathways. This study may provide new insights into the association among OT intervention, host gut microbiome and metabolic profile, and improve the knowledge of clinical strategies and personalized nutrition.


Total prosthetic replacement of ankylosed knees.
Total knee arthroplasty is reliable for achieving pain relief, increasing range of motion, maintaining stability, and improving walking ability. In this study, the results in knees with a preoperative range of motion of 0 were reviewed to determine whether an ankylosed knee can be replaced successfully. In eight of nine knees, the results with regard to pain, stability, and walking ability were good at follow-up evaluations greater than 2 years after operation. Range of motion was also improved in all knees but was still limited. Motion achieved was in a physiologic arc with all knees having full, or nearly full, extension.


Automatically showing microbial growth kinetics with a high-performance microbial growth analyzer.
It is difficult to show microbial growth kinetics online when they grow in complex matrices. We presented a novel strategy to address this challenge by developing a high-performance microbial growth analyzer (HPMGA), which employed a unique 32-channel capacitively coupled contactless conductivity detector as a sensing element and fixed with a CellStatz software. It was capable of online showing accurate and repeatable growth curves of well-dispersed and bad-dispersed microbes, whether they grew in homogeneous simple culture broth or heterogeneous complex matrices. Moreover, it could automatically report key growth kinetics parameters. In comparison to optical density (OD), plate counting and broth microdilution (BMD) methods, we demonstrated its practicability in five scenarios: 1) the illustration of the growth, growth rate, and acceleration curves of Escherichia coli (E. coli); 2) the antimicrobial susceptibility testing (AST) of Oxacillin against Staphylococcus aureus (S. aureus); 3) the determination of Ag nanoparticle toxicity on Providencia rettgeri (P. rettgeri); 4) the characterization of milk fermentation; and 5) the enumeration of viable pathogenic Vibrio in shrimp body. Results highlighted that the HPMGA method had the advantages of universality and effectivity. This technology would significantly facilitate the routine analysis of microbial growth in many fields (biology, medicine, clinic, life, food, environment, and ecology), paving an avenue for microbiologists to achieve research goals that have been inhibited for years due to a lack of practical analytical methods.


Quantitative sequencing clarifies the role of disruptor taxa, oral microbiota, and strict anaerobes in the human small-intestine microbiome.
Upper gastrointestinal (GI) disorders and abdominal pain afflict between 12 and 30% of the worldwide population and research suggests these conditions are linked to the gut microbiome. Although large-intestine microbiota have been linked to several GI diseases, the microbiota of the human small intestine and its relation to human disease has been understudied. The small intestine is the major site for immune surveillance in the gut, and compared with the large intestine, it has greater than 100 times the surface area and a thinner and more permeable mucus layer. Using quantitative sequencing, we evaluated total and taxon-specific absolute microbial loads from 250 duodenal-aspirate samples and 21 paired duodenum-saliva samples from participants in the REIMAGINE study. Log-transformed total microbial loads spanned 5 logs and were normally distributed. Paired saliva-duodenum samples suggested potential transmission of oral microbes to the duodenum, including organisms from the HACEK group. Several taxa, including Klebsiella, Escherichia, Enterococcus, and Clostridium, seemed to displace strict anaerobes common in the duodenum, so we refer to these taxa as disruptors. Disruptor taxa were enriched in samples with high total microbial loads and in individuals with small intestinal bacterial overgrowth (SIBO). Absolute loads of disruptors were associated with more severe GI symptoms, highlighting the value of absolute taxon quantification when studying small-intestine health and function. This study provides the largest dataset of the absolute abundance of microbiota from the human duodenum to date. The results reveal a clear relationship between the oral microbiota and the duodenal microbiota and suggest an association between the absolute abundance of disruptor taxa, SIBO, and the prevalence of severe GI symptoms. Video Abstract.


ATLANTIS trial: results for patients treated within 3 hours of stroke onset. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke.
Only a single study has demonstrated beneficial effects of intravenous tissue plasminogen activator (tPA) in stroke patients. We evaluated the clinical outcomes of the 61 patients enrolled in the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study who were randomized to receive intravenous tPA or placebo within 3 hours of symptom onset. Despite a significant increase in the rate of symptomatic intracranial hemorrhage, tPA-treated patients were more likely to have a very favorable outcome (score of < or = 1) on the National Institutes of Health Stroke Scale at 90 days (P=0.01). These data support current recommendations to administer intravenous tPA to eligible ischemic stroke patients who can be treated within 3 hours of symptom onset.


Synthesis and biological activities of methyl oligobiosaminide and some deoxy isomers thereof.
Methyl oligobiosaminide (1) the core structure of oligostatin C, and five analogues, the 6-hydroxy-(2), 2-deoxy- (3), 2-deoxy-6-hydroxy- (4), 3-deoxy- (5), and 3-deoxy-6-hydroxy derivatives (6), were synthesized by coupling the protected pseudo-sugar epoxide 46 with suitable methyl 4-amino-4-deoxy-alpha-D-hexopyranoside derivatives. Compounds 3 and 6 showed notable inhibitory activity against alpha-D-glucosidase and alpha-D-mannosidase, respectively, whereas compound 1 had almost no activity.


Conversion mechanisms between organic sulfur and inorganic sulfur in surface sediments in coastal rivers.
Geochemical processes of sulfur (S) in river aquatic systems play a crucial role in environmental evolution. In this study, the distributions and sources of reduced inorganic sulfur (RIS) and organic sulfur (OS) in coastal river surface sediments were investigated. The results indicated that OS dominated total S (80%), and OS (i.e., humic acid sulfur, HAS; fulvic acid sulfur, FAS) correlated with the availability of labile organic matter (OM) and reactive iron (Fe). Terrigenous inputs and sulfurization contributed to the enrichment of FAS through the S reduction. Autochthonous biological inputs were potential sources of HAS from S oxidization. The X-ray photoelectron spectroscopy showed that the main sources of S in surface sediments were deposited as the form of organic ester-sulfate. Aquatic life could break S down further, producing reduced S compounds accumulated as thiols and RIS in anoxic sediments. RIS was dominated by acid volatile sulfur (AVS) and chromium (II)-reducible sulfur (CRS). Reactive Fe oxides were major control factors for the conversation from hydrogen sulfide (H2S) to AVS, whereas elemental sulfide (ES) controlled the conversion from AVS into CRS in coastal rivers.


C-to-U conversion in the intercistronic ndhI/ ndhG RNA of plastids from monocot plants: conventional editing in an unconventional small reading frame?
Editing of plastid RNAs proceeds by C-to-U, in hornwort species also by extensive U-to-C, transitions, which predominantly lead to the restoration of codons for structurally and/or functionally important, conserved amino acid residues. So far, only one instance of editing outside coding regions has been reported - in the psbL/ psbF intergenic region of Ginkgo biloba. This site was proposed to have no functional importance. Here we present an evaluation of an editing site in the ndhI/ ndhG intergenic region in a related group of monocot plants. Efficient editing of this site, as well as the phylogenetic conservation of the resulting uridine residue, point at an important role for the sequence restored by editing. Two potential functions can be envisaged. (1) RNA secondary structure predictions suggest that the C-to-U conversion at this site can lead to a modified stem/loop structure of the ndhG 5' UTR, which could influence ndhG expression. (2) Alternatively, editing of the ndhI/ ndhG intergenic region may tag a so far unidentified small (12-codon) ORF, and lead to the restoration of a conserved phenylalanine codon. A screen with specific antibodies elicited against the putative peptide failed to detect such a peptide in chloroplast fractions. However, this failure may be attributable to its low and/or development-specific expression.


Significantly Greater Progression of Intima-Media Thickness of the Carotid Artery in Japanese American Men Than in White Men: The ERA JUMP Study.
Although a westernized lifestyle was associated with increased coronary heart disease (CHD), morbidity, and mortality in first- and second-generation Japanese Americans, CHD mortality was reported to be lower in this population than in whites. The risk profile of CHD for third- and fourth-generation Japanese Americans is not known. We compared the progression of carotid intima-media thickness (CIMT) between third- or fourth-generation Japanese Americans and whites. Population-based samples of 473 men (Japanese Americans, 227; whites, 246) aged 40-49 years at baseline and free of clinical cardiovascular disease were examined for CIMT at baseline (2004-2007) and follow-up (2007-2013). CIMT was determined centrally at the University of Pittsburgh, Pittsburgh, Pennsylvania. Analysis of covariance was used to compare annualized progression of CIMT between Japanese Americans and whites, adjusting for cardiovascular risk factors and baseline CIMT. Progression of CIMT was significantly greater in Japanese Americans than in whites both before and after adjusting for covariates: mean, 14.4 μm/y; 95% confidence interval [CI],12.3-16.4 vs 9.8 μm/y; 95% CI, 7.8-11.7; P < 0.05 and 15.1 μm/y; 95% CI, 13.1-17.1 vs 9.1 μm/y; 95% CI, 7.2-11.0; P < 0.05, respectively. Age, total cholesterol/high-density lipoprotein cholesterol, and diabetes in Japanese Americans and age, hypertension, and lipid medication in whites were significantly associated with progression of CIMT. The significantly greater progression of CIMT in Japanese Americans than in whites might suggest a higher future burden of CHD in Japanese Americans than in whites. The current study identifies Japanese Americans as an important target group for prevention of CHD. Future research assessing carotid plaque in addition to CIMT is warranted.


Pancreatic cystic lesions and the role of contrast enhanced endoscopic ultrasound.
An exponential rise in the use of cross-sectional imaging has led to an increase in the incidental identification of pancreatic cystic lesions (PCL); however, with many subtypes defined to date and heterogeneous morphology with often absent defining radiological features, PCLs present a diagnostic challenge. Computed tomography (CT) and/or magnetic resonance imaging (MRI) alone are frequently not sufficient to provide accurate characterisation. Endoscopic ultrasound (EUS) has an important role in the evaluation and classification of PCLs through its ability to define the internal architecture, which is further enhanced by the use of contrast medium. It is also used widely for the surveillance of larger cysts (>2 cm), which are associated with a greater malignant potential. The aim of this review is to demonstrate the role of contrast-enhanced (CE)-EUS in the diagnosis and risk stratification of PCLs. The features of the main non-neoplastic and neoplastic PCLs observed on CE-EUS are provided. When used in combination with other imaging techniques and patient characteristics, CE-EUS offers a more accurate assessment of PCLs and aids risk stratification. Additionally, CE-EUS enables assessment of parenchymal perfusion improving the precision of cyst characterisation and targeted biopsy of worrisome components. The International Consensus Guidelines recommend regular follow up for patients with mucinous or indeterminate PCLs that are fit enough for surgery. With the growing range of tools available to assess PCLs including CE-EUS, it is hoped that patients can be steered towards surgery, surveillance, or discharge with increasing accuracy.


Alignment of displaced or impacted teeth with the traction chain.
To align those teeth in the dental arch that cannot erupt or are displaced, they must be surgically exposed. After the traction device is attached, the tooth is again covered with the mucoperiosteal flap to protect the tissues involved. For this reason, the loss of this traction device must be absolutely avoided in order to prevent another surgical intervention. Here at the University of Ulm, we have developed and tested an optimized traction chain for that purpose. The chain is attached to the tooth with a laser-roughened pad applying the acid-etching technique. The chain links serve as fixation elements for traction devices such as elastic ligatures or piggyback archwires. At the same time, one can determine the distance covered by the tooth by the number of the erupting chain links. We demonstrate the clinical application of this traction device in two cases.


Inclination of mandibular incisors and symphysis in severe skeletal class III malocclusion.
The aim of this study was to systematically explore the inclination of the lower central incisor and symphysis in alveolar bone in severe skeletal class III patients. A total of 198 severe skeletal class III patients (ANB ≤ -4°) who underwent combined orthodontic and orthognathic treatment were divided into three groups based on the mandibular plane angle (MP-SN). Pretreatment lateral cephalograms were analysed and compared among the three groups. We also assessed cone-beam computed tomography (CBCT) images of 11 samples to investigate the reliability of the cephalometric analysis. ANOVA showed no statistically significant differences in the angle between the long axis of the mandibular symphysis and the long axis of the lower central incisor (MIA) among the low-angle, normal-angle and high-angle groups (P > 0.05), while significant differences were found in the angle between the axis of the lower incisor and the mandibular plane (IMPA) among the three groups (P < 0.001). The mean IMPA decreased with increasing MP-SN in the 198 patients. The mean MIA in the low-angle and normal-angle groups was 3.70° and 3.52°, respectively, while the value (2.33°) was smaller in the high-angle group. Paired-samples t test showed no statistically significant differences between the cephalometric and CBCT measurements of the MP-SN, the angle between the mandibular plane and the Frankfort plane (FH-MP) and the MIA (P > 0.05). In severe skeletal class III patients, the long axis of the lower central incisor was highly consistent with the long axis of the mandibular symphysis, which was more obvious in the high-angle subjects. The MIA reflects the physiological inclination of the lower central incisor better than the IMPA.


Superior mesenteric venous thrombosis associated with a familial missense mutation (Pro626Leu) in the SHBG-like domain of the protein S molecule.
A 76-year-old Japanese woman was hospitalized for ileus symptoms caused by extensive thrombosis of the superior mesenteric vein. Because laboratory test results suggested type III protein S (PS) deficiency, molecular changes in PS were investigated. A single-base transition, CCG to CTG at codon 626 in exon XV, resulting in the missense mutation Pro626Leu, was identified in an allele of the patient and in her son. Reverse transcriptase polymerase chain reaction analysis indicated the presence of both normal and mutant types of PS messages in platelet-derived messenger RNAs. Our findings thus suggest that Pro626 in SHBG-like domain 7 may be crucial for in vivo antithrombotic activity of the PS molecule.