Modeling Brain Volume Using Deep Learning-Based Physical Activity Features in Patients With Dementia.
There is a proven correlation between the severity of dementia and reduced brain volumes. Several studies have attempted to use activity data to estimate brain volume as a means of detecting reduction early; however, raw activity data are not directly interpretable and are unstructured, making them challenging to utilize. Furthermore, in the previous research, brain volume estimates were limited to total brain volume and the investigators were unable to detect reductions in specific regions of the brain that are typically used to characterize disease progression. We aimed to evaluate volume prediction of 116 brain regions through activity data obtained combining time-frequency domain- and unsupervised deep learning-based feature extraction methods. We developed a feature extraction model based on unsupervised deep learning using activity data from the National Health and Nutrition Examination Survey (NHANES) dataset (n = 14,482). Then, we applied the model and the time-frequency domain feature extraction method to the activity data of the Biobank Innovations for chronic Cerebrovascular disease With ALZheimer's disease Study (BICWALZS) datasets (n = 177) to extract activity features. Brain volumes were calculated from the brain magnetic resonance imaging of the BICWALZS dataset and anatomically subdivided into 116 regions. Finally, we fitted linear regression models to estimate each regional volume of the 116 brain areas based on the extracted activity features. Regression models were statistically significant for each region, with an average correlation coefficient of 0.990 ± 0.006. In all brain regions, the correlation was > 0.964. Particularly, regions of the temporal lobe that exhibit characteristic atrophy in the early stages of Alzheimer's disease showed the highest correlation (0.995). Through a combined deep learning-time-frequency domain feature extraction method, we could extract activity features based solely on the activity dataset, without including clinical variables. The findings of this study indicate the possibility of using activity data for the detection of neurological disorders such as Alzheimer's disease.


Reconsidering the absence of extrapancreatic extension in T staging for pancreatic adenocarcinoma in the AJCC (8th ed) Staging Manual using the National Cancer Database.
Although the concept of extrapancreatic extension (EPEx) was removed in the eighth edition of the American Joint Committee on Cancer pancreatic cancer staging system, several studies have supported the prognostic significance of EPEx. This study aimed to investigate the significance of EPEx in pancreatic ductal adenocarcinoma (PDAC) using the National Cancer Database (NCDB). Data of patients who underwent resection for PDAC between 2006 and 2016 were extracted and analyzed from the NCDB. Cases arising from premalignant lesions, those with metastases, and those treated with neoadjuvant therapy were excluded. Among 37,634 patients, the median overall survival was 23 months and the 5-year survival rate was 22.7%. The EPEx prevalence was the lowest for T1 stage (63.2%) and increased with each T-stage (T2:83.4%, T3:85.8%). The overall survival was better in EPEx-negative patients than in EPEx-positive patients (median 33.7 vs. 21.5 months; p<0.001). When the T-stages were stratified by EPEx, EPEx-positive patients showed worse survival in all T-stages than EPEx-negative patients. Survival was comparable between T1 EPEx-positive and T2 or T3 EPEx-negative patients (p=0.088 and p=0.178, respectively). Furthermore, T2 and T3 EPEx-negative patients had similar survival to each other (p=0.877), and distinctly superior survival compared to T2 and T3 EPEx-positive patients (p<0.001). EPEx was an important prognostic factor in the overall cohort and in differentiating between T stages. This study strongly suggests that staging systems should reinstate EPEx and apply it to all T-stages, especially in T1, where EPEx was absent in 36% of patients.


Psychophysical therapy and underlying neuroendocrine mechanisms for the rehabilitation of long COVID-19.
With the global epidemic and prevention of the COVID-19, long COVID-19 sequelae and its comprehensive prevention have attracted widespread attention. Long COVID-19 sequelae refer to that three months after acute COVID-19, the test of SARS-CoV-2 is negative, but some symptoms still exist, such as cough, prolonged dyspnea and fatigue, shortness of breath, palpitations and insomnia. Its pathological mechanism is related to direct viral damage, immunopathological response, endocrine and metabolism disorders. Although there are more effective methods for treating COVID-19, the treatment options available for patients with long COVID-19 remain quite limited. Psychophysical therapies, such as exercise, oxygen therapy, photobiomodulation, and meditation, have been attempted as treatment modalities for long COVID-19, which have the potential to promote recovery through immune regulation, antioxidant effects, and neuroendocrine regulation. Neuroendocrine regulation plays a significant role in repairing damage after viral infection, regulating immune homeostasis, and improving metabolic activity in patients with long COVID-19. This review uses oxytocin as an example to examine the neuroendocrine mechanisms involved in the psychophysical therapies of long COVID-19 syndrome and proposes a psychophysical strategy for the treatment of long COVID-19.


FM Combined With NIHSS Score Contributes to Early AIS Diagnosis and Differential Diagnosis of Cardiogenic and Non-Cardiogenic AIS.
A growing researchers have suggested that fibrin monomer (FM) plays an important role in early diagnosis of thrombotic diseases. We explored the application of FM in the diagnosis and classification of acute ischemic stroke (AIS). The differences in FM, D-dimer, and NIHSS scores between different TOAST (Trial of ORG 10172 in Acute Stroke Treatment) types were analyzed with one-way ANOVA; the correlation between FM, D-dimer and NIHSS score in patients with different TOAST classification was analyzed by Pearson linear correlation. The ROC curve was utilized to analyze the diagnostic performance. 1. FM was more effective in diagnosing patients with AIS than D-dimer. 2. The FM level in cardiogenic AIS was significantly different from that in non-cardiogenic patients (P < 0.05); the NIHSS score in cardiogenic stroke was significantly higher than in atherosclerotic and unexplained stroke group. Whereas, no statistical difference was observed in the D-dimer level between these groups (P > 0.05). 3. The correlation between FM and NIHSS scores in the cardiogenic (r = 0.3832) and atherosclerotic (r = 0.3144) groups was statistically significant. 4. FM exhibited the highest diagnostic efficacy for cardiogenic AIS; furthermore, FM combined with the NIHSS score was more conducive to the differential diagnosis of cardiogenic and non-cardiogenic AIS. FM detection contributes to the early diagnosis of AIS, and is important for the differential diagnosis of different TOAST types of AIS. Moreover, FM combined with the NIHSS score is valuable in the differential diagnosis of cardiogenic and non-cardiogenic AIS.


Use of Gene Ontology Annotation to understand the peroxisome proteome in humans.
The Gene Ontology (GO) is the de facto standard for the functional description of gene products, providing a consistent, information-rich terminology applicable across species and information repositories. The UniProt Consortium uses both manual and automatic GO annotation approaches to curate UniProt Knowledgebase (UniProtKB) entries. The selection of a protein set prioritized for manual annotation has implications for the characteristics of the information provided to users working in a specific field or interested in particular pathways or processes. In this article, we describe an organelle-focused, manual curation initiative targeting proteins from the human peroxisome. We discuss the steps taken to define the peroxisome proteome and the challenges encountered in defining the boundaries of this protein set. We illustrate with the use of examples how GO annotations now capture cell and tissue type information and the advantages that such an annotation approach provides to users. Database URL: http://www.ebi.ac.uk/GOA/ and http://www.uniprot.org.


Birchall and Benwell. Murder in a Canadian swamp.
On 21 February 1890, two woodsmen working in densely wooded Blenheim Swamp in southern Ontario, Canada, stumbled upon the dead body of a young Englishman who had been killed by two gunshot wounds to the head. He was identified as Frederick Benwell by a married couple, the Birchalls, who had traveled with him and another man, Pelly, from England to New York City by ship about 1 week before. The Birchalls lied regarding Benwell's subsequent movements. Questioning Pelly revealed to Detective John Murray that both Pelly and Benwell had replied separately to Birchall's advertisement for young men of means to become partners with him in a large Canadian farm, a deposit first being required. Birchall had been observed taking Benwell from Buffalo, New York, to Blenheim Swamp, for in reality there was no farm. There he had shot Benwell, leaving the body partially exposed. He then tried unsuccessfully to lure Pelly to his death in Niagara Falls. The Birchalls were arrested. Reginald Birchall was tried, convicted, and hanged. His attempt, including murder, to turn the so-called farm pupil colonization scheme to his own benefit had been frustrated by the dogged work of the master Canadian detective Murray.


Age has a U-shaped relationship with breast cancer outcomes in women: a cohort study.
Age is a significant determinant of susceptibility to breast cancer. Currently, the available evidence regarding the non-linear correlation between the age of diagnosis and the prognosis of breast cancer patients is contradictory. Insufficient data currently exist regarding the influence of age at diagnosis on the prognosis of breast cancer. The objective of our investigation was to examine the relationship between age at diagnosis and overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). This retrospective cohort study included 1054 patients diagnosed with breast cancer between March 7, 2013 and December 31, 2019. The hazard ratios (HRs) and 95% confidence interval (CI) for OS, BCSS, DFS were assessed using Cox proportional hazard ratio models and restricted cubic splines (RCS). The study included 1054 breast cancer patients who met the criteria. With a median follow-up of 4.86 years, 71 patients (6.74%) died and 144 patients (13.66%) relapsed. After multivariable adjustment, age showed a U-shaped association with OS, BCSS, and DFS, with significantly higher risk at two ends, with age inflection points of 44, 44, and 41 years for OS, BCSS, and DFS, respectively. For OS, Quartile 1 (HR, 2.09; 95% CI: 0.90-4.84), Quartile 3 (HR, 2.44; 95% CI: 1.05-5.65) and Quartile 4 (HR, 3.38; 95% CI: 1.51-7.54) had poorer OS compared with Quartile 2. Similar results were found for BCSS and DFS. This study confirmed a U-shaped association between age at diagnosis and breast cancer outcome.


Effect of aldehyde dehydrogenase inhibitors on the ex vivo sensitivity of human multipotent and committed hematopoietic progenitor cells and malignant blood cells to oxazaphosphorines.
The ex vivo sensitivity of human multipotent and committed hematopoietic progenitor cells and several cultured human malignant blood cell lines to analogues of "activated" cyclophosphamide, namely, 4-hydroperoxycyclophosphamide and mafosfamide, and to phosphoramide mustard was quantified with and without concurrent exposure to an inhibitor of aldehyde dehydrogenase activity, namely, disulfiram, cyanamide, diethyldithiocarbamate, or ethylphenyl(2-formylethyl)phosphinate. Inhibitors of aldehyde dehydrogenase activity potentiated the cytotoxic action of 4-hydroperoxycyclophosphamide and mafosfamide toward all of the hematopoietic progenitors; they did not potentiate the cytotoxic action of phosphoramide mustard toward these cells. Potentiation of the cytotoxic action of mafosfamide toward cultured human malignant blood cells was minimal. Spectrophotometric assay revealed little NAD-linked aldehyde dehydrogenase activity present in the cultured human tumor cell lines as compared to that found in normal mouse liver or oxazaphosphorine-resistant L1210 cells. Cellular aldehyde dehydrogenases are known to catalyze the oxidation of 4-hydroxycyclophosphamide/aldophosphamide, the major intermediate in cyclophosphamide bioactivation, to the relatively nontoxic acid, carboxyphosphamide. Thus, our findings indicate that human multipotent hematopoietic progenitor cells contain the relevant aldehyde dehydrogenase activity, the relevant activity is retained upon differentiation to progenitors committed to the megakaryocytoid, granulocytoid/monocytoid, and erythroid lineages, and the relevant activity may be lost or diminished upon transformation of hematopoietic progenitors to malignant cells.


Social Gradients and Physical Activity Trends in an Obesogenic Dietary Pattern: Cross-Sectional Analysis of the UK National Diet and Nutrition Survey 2008-2014.
An energy-dense, high-fat, low-fibre dietary pattern has been prospectively associated with the development of obesity in childhood but is population-specific, which limits translating the pattern into interventions. We explored the generalisability and correlates of this obesogenic dietary pattern in the UK National Diet and Nutrition Survey (NDNS) for the first time. Data came from participants (n = 4636 children and n = 4738 adults) with 4-day food diaries in NDNS 2008-2014. Reduced rank regression was applied to 51 food groups to explain variation in energy density, fibre and fat intake. Consistency of the pattern in population subgroups (according to sex, age, occupation and income) was compared with the whole sample pattern using coefficients of congruence (COC). Pattern correlates (sociodemographic, survey year, physical activity and eating related behaviours) were explored using multiple linear regression. Food group loadings were similar to the previously identified obesogenic dietary pattern and were generalisable across all sub-groups (COC: 0.93-0.99). An obesogenic diet was associated with eating takeaways, being omnivorous, a manual household occupation and lower household income in both adults and children (p < 0.0001). Dieting for weight loss, being older, more physically active and less sedentary was associated with a less obesogenic diet among adults (p < 0.0001). Future experimental studies should investigate if changes in this obesogenic pattern could be used to monitor the effectiveness of obesity prevention policies or develop personalised interventions.


Oxidative DNA and RNA damage in rat liver due to acetoxime: similarity to effects of 2-nitropropane.
Acetoxime (ACO) and 2-nitropropane (2-NP), both industrially important chemicals and known hepatocarcinogens in rats, induced increased levels of 8-hydroxy-guanine in liver DNA and RNA of male Sprague-Dawley and F344 rats after either oral or i.p. administration. Both compounds also produced qualitatively the same patterns of other apparent modifications of liver DNA and RNA nucleosides, discernible by HPLC with electrochemical detection. Six hours after administration, the effects of 2-NP on liver nucleic acids were more pronounced in F344 rats than in Sprague-Dawley rats, suggesting that 2-NP may prove to be a stronger carcinogen in the F344 strain. The effects of ACO, a weaker carcinogen than 2-NP, were less than those of the nitroalkane in both rat strains. These results suggest that the hepatocarcinogenicity of ACO, like that of 2-NP, may depend on increased generation of reactive oxygen species capable of producing DNA and RNA base damage in rat liver. In addition, the data support the hypothesis that the hepatocarcinogenicity of ACO depends on its partial in vivo N-oxidation to 2-NP.


Child feeding and human rights.
The human right to adequate food needs to be interpreted for the special case of young children because they are vulnerable, others make the choices for them, and their diets are not diverse. There are many public policy issues relating to child feeding. The core of the debate lies in differences in views on the merits of infant formula. In contexts in which there is strong evidence and a clear consensus that the use of formula would be seriously dangerous, it might be sensible to adopt rules limiting its use. However, until there is broad consensus on this point, the best universal rule would be to rely on informed choice by mothers, with their having a clearly recognized right to objective and consistent information on the risks of using different feeding methods in their particular local circumstances. The obligation of the state to assure that mothers are well informed should be viewed as part of its broader obligation to establish social conditions that facilitate sound child feeding practices. This means that mothers should not be compelled to feed in particular ways by the state, but rather the state should assure that mothers are supported and enabled to make good feeding choices.Thus, children should be viewed as having the right to be breastfed, not in the sense that the mother is obligated to breastfeed the child, but in the sense that no one may interfere with the mother's right to breastfeed the child. Breastfeeding should be viewed as the right of the mother and child together.


Adenosine 3':5'-cyclic monophosphate induces regulated secretion of tissue-type plasminogen activator and von Willebrand factor from cultured human endothelial cells.
The effect of compounds increasing intracellular adenosine 3':5'-cyclic monophosphate [cAMP]i levels (prostacyclin, isoproterenol, forskolin, cholera toxin), and of the cAMP analogs 8-bromo-cAMP and dibutyryl-cAMP, on the regulated secretion (acute release) of tissue-type plasminogen activator (tPA) and von Willebrand factor (vWF) was studied in cultured human umbilical vein endothelial cells (HUVEC). Prostacyclin, isoproterenol and forskolin, which increased [cAMP]i in HUVEC, and the cell-permeant cAMP analog 8-bromo-cAMP induced dose- and time-dependent secretion of tPA and vWF. The extent of vWF and tPA release correlated with [cAMP]i, and was increased by the phosphodiesterase inhibitor isobutylmethylxanthine. In contrast to thrombin, the cAMP-elevating agents did not increase the intracellular calcium concentration [Ca2+]i in HUVEC. At submaximal concentrations, the effects of thrombin and prostacyclin were additive. Our results show that an increase in [cAMP]i resulted in regulated secretion (acute release) of tPA and vWF from HUVEC, without the concomitant increase in [Ca2+]i which is, in HUVEC, essential for thrombin-induced regulated secretion to occur. cAMP-induced secretion represents a novel mechanism for causing regulated secretion of tPA and vWF from endothelial cells.


Mechanisms of specificity of association between the nematode Steinernema scapterisci and its symbiotic bacterium.
We suggest a new mechanism for the maintenance of specificity of the association between the entomopathogenic nematode Steinernema scapterisci and its symbiotic bacteria. We evaluated the development and reproduction of infective and non-infective juvenile S. scapterisci in monoxenic combinations with its symbiotic bacteria, Xenorhabdus sp. 'S' and with the bacterial symbiont of Steinernema carpocapsae and Steinernema riobravis. Although development of non-infective stages occurred on all Xenorhabdus spp., the development of infective juveniles to the 4th stage ('dauer' recovery) was significantly delayed and reduced with X. nematophilus and Xenorhabdus sp. 'R', the bacterial symbionts of S. carpocapsae and S. riobravis, respectively. 'Dauer' recovery improved significantly when the cultures of X. nematophilus and Xenorhabdus sp. 'R' were supplemented with cell-free filtrates from Xenorhabdus sp. 'S'. The infective juvenile S. scapterisci produced in all 3 cultures were virulent to Galleria mellonella larvae, confirming successful retention of Xenorhabdus from other steinernematids in their intestine. In fact, S. scapterisci infective juveniles containing X. nematophilus or Xenorhabdus sp. 'R' were more virulent to G. mellonella than those containing their natural symbiont, Xenorhabdus sp. 'S'. We believe that this is the first demonstration of the symbiont-specific exit of infective juveniles from the 'dauer' phase which represents the finest level of specificity of bacteria-nematode association. This is also the first report of successful isolation of the natural symbiont of S. scapterisci.


County-Level Soybean Yield Prediction Using Deep CNN-LSTM Model.
Yield prediction is of great significance for yield mapping, crop market planning, crop insurance, and harvest management. Remote sensing is becoming increasingly important in crop yield prediction. Based on remote sensing data, great progress has been made in this field by using machine learning, especially the Deep Learning (DL) method, including Convolutional Neural Network (CNN) or Long Short-Term Memory (LSTM). Recent experiments in this area suggested that CNN can explore more spatial features and LSTM has the ability to reveal phenological characteristics, which both play an important role in crop yield prediction. However, very few experiments combining these two models for crop yield prediction have been reported. In this paper, we propose a deep CNN-LSTM model for both end-of-season and in-season soybean yield prediction in CONUS at the county-level. The model was trained by crop growth variables and environment variables, which include weather data, MODIS Land Surface Temperature (LST) data, and MODIS Surface Reflectance (SR) data; historical soybean yield data were employed as labels. Based on the Google Earth Engine (GEE), all these training data were combined and transformed into histogram-based tensors for deep learning. The results of the experiment indicate that the prediction performance of the proposed CNN-LSTM model can outperform the pure CNN or LSTM model in both end-of-season and in-season. The proposed method shows great potential in improving the accuracy of yield prediction for other crops like corn, wheat, and potatoes at fine scales in the future.


Dual-targeted anti-TB/anti-HIV heterodimers.
HIV and M. tuberculosis are two intersecting epidemics making the search for new dual action drugs against both pathogens extremely important. Here, we report on the synthesis and suppressive activities of five dual-targeted HIV/TB compounds. These compounds are heterodimers of AZT, as anti-HIV molecules, and 5-substituted uracil derivatives, as anti-TB molecules. We found that these compounds inhibit the growth of M. tuberculosis and suppress the replication of HIV in human cell cultures and human lymphoid tissues ex vivo. We identified one particular heterodimer that inhibited both HIV and the drug-resistant TB strain MS-115 most potently. This compound demonstrated low toxicity and had no cytostatic effect on cells in culture, constituting an ideal candidate for future development and further in vivo testing.


Nonlinearity of the Jongkees difference equation for vestibular hypofunction.
The Jongkees formulation for vestibular paresis normalizes the difference between total left and right caloric responses to the sum of responses. When studied over the full paresis range of 0% to 100% hypofunction, the Jongkees formula is found to be a nonlinear index that does not accurately indicate the percentage of vestibular paresis. A linear paresis formula is described that more directly conveys the magnitude of relative vestibular hypofunction.


Human antibody responses to a Chlamydia-secreted protease factor.
We have previously identified a chlamydia-secreted protein (designated chlamydial proteasome/protease-like activity factor, or CPAF) in the cytosol of chlamydia-infected cells. Although CPAF is known to degrade host transcription factors required for major histocompatibility complex antigen expression in cultured cells, it is not clear whether CPAF is produced and maintains similar functions in humans infected with chlamydial organisms. We now report that CPAF does not preexist in chlamydial organisms and that CPAF synthesis requires live organism replication in cultured cells. Mice inoculated with live, but not mice inoculated with dead, chlamydial organisms produced a strong antibody response to CPAF, correlating CPAF-specific antibody production with CPAF synthesis in animals. Sera from women diagnosed with Chlamydia trachomatis cervicitis displayed higher levels of antibodies to CPAF than to either chlamydial major outer membrane protein or heat shock protein 60, suggesting that CPAF is both produced and immunogenic during human chlamydial infection.


Salmonella choleraesuis strains deficient in O antigen remain fully virulent for mice by parenteral inoculation but are avirulent by oral administration.
O-antigen-deficient derivatives of two mouse-virulent strains of Salmonella choleraesuis (serogroup C1; O-6,7) were constructed by transduction of a long deletion of the rfb operon. Strains SN36 and SN57 were derived from the smooth ancestor SL2824, while SN37 was derived from the smooth ancestor SL2840. These rfb deletion derivatives (rfb strains) had typical bacteriophage sensitivity patterns of "rough" Salmonella strains and were at least 200,000 times more sensitive to serum than their smooth ancestors. Lipopolysaccharides (LPS) extracted from them consisted only of two low-molecular-weight bands and lacked the ladderlike pattern of bands seen in the LPS of their smooth ancestors. The LPS from the rfb strains did not react in an enzyme immunoassay with any of three monoclonal antibodies directed against different epitopes of the O-6,7 antigen but reacted well with at least one of three monoclonal antibodies specific for core epitopes. The data were consistent with inability of these strains to synthesize O-specific chains and showed that the LPS extracted from SN57 was of chemotype Ra and that from SN36 was of chemotype Rb1, while that of SN37 consisted of a mixture of the two chemotypes. The virulence of these strains was tested by various routes in BALB/c mice. All three O-antigen-deficient derivatives were about as virulent as their "smooth" ancestors by the intraperitoneal and intravenous routes (50% lethal dose, 20 to 700 bacteria) but, unlike their ancestors, were avirulent by the oral route (50% lethal dose, greater than or equal to 5 x 10(9) bacteria). This suggests that the major role of smooth LPS in the mouse virulence of S. choleraesuis is to facilitate survival in the gastrointestinal tract and eventual entry into deeper tissues.


Rapid visual detection of Aeromonas salmonicida by loop-mediated isothermal amplification with hydroxynaphthol blue dye.
To make crucial prevention, reduce fish losses and minimize the economic damage of diseases on the fish farm owners, a rapid detection of fish pathogens is mandatory. In this study, a loop-mediated isothermal amplification assay combined with hydroxynaphthol blue dye (LAMP-HNB) was developed and used for the rapid detection of Aeromonas salmonicida that caused significant economic losses in fish farming. Firstly, a pair of outer and inner primers specific for conserved fragment of vapA gene in A. salmonicida were designed and synthesized. Secondly, by optimizing the reaction conditions including reaction temperature, time, Mg2+ concentration, dNTP concentration and primer ratio, a LAMP-HNB assay was successfully established for the detection of A. salmoncida. Thirdly, the assay showed good specificity with no false-positive and false-negative results, and good sensitivity with the detection limit of 3.077 × 10-6 ng/μl, which was 102 times more sensitive than the conventional PCR. Finally, the LAMP-HNB assay was validated by the fish samples inoculated with different concentrations of A. salmoncida. This is the first development of rapid visual detection of A. salmonicida based on LAMP-HNB assay, which has great application prospect and market for diagnostic testing, health certification and active surveillance programmers.


Inhibition of K+ outward currents by linopirdine in the cochlear outer hair cells of circling mice within the first postnatal week.
Inhibition of K+ outward currents by linopirdine in the outer hair cells (OHCs) of circling mice (homozygous (cir/cir) mice), an animal model for human deafness (DFNB6 type), was investigated using a whole cell patch clamp technique. Littermate heterozygous (+/cir) and ICR mice of the same age (postnatal day (P) 0 -P6) were used as controls. Voltage steps from -100 mV to 40 mV elicited small inward currents (-100 mV~-70 mV) and slow rising K+ outward currents (-60 mV ~40 mV) which activated near -50 mV in all OHCs tested. Linopirdine, a known blocker of K+ currents activated at negative potentials (IK,n), did cause inhibition at varying degree (severe, moderate, mild) in K+ outward currents of heterozygous (+/cir) or homozygous (cir/cir) mice OHCs in the concentration range between 1 and 100 µM, while it was apparent only in one ICR mice OHC out of nine OHCs at 100 µM. Although the half inhibition concentrations in heterozygous (+/cir) or homozygous (cir/cir) mice OHCs were close to those reported in IK,n, biophysical and pharmacological properties of K+ outward currents, such as the activation close to -50 mV, small inward currents evoked by hyperpolarizing steps and TEA sensitivity, were not in line with IK,n reported in other tissues. Our results show that the delayed rectifier type K+ outward currents, which are not similar to IK,n with respect to biophysical and pharmacological properties, are inhibited by linopirdine in the developing (P0~P6) homozygous (cir/cir) or heterozygous (+/cir) mice OHCs.


Comparison of glucose tolerance, lipids and blood pressure in young male Ethiopians from two different immigrations, 1989 and 1991.
The prevalence of glucose intolerance and hypertension was compared between a group of 87 young Ethiopian males (age 21.6 +/- 2.8 years) from the post Moses immigration of 1989 (group 1) and 89 age-matched Ethiopian males (age 21.4 +/- 3.1) from the Solomon immigration of 1991 (group 2). Both groups demonstrated a relatively high, for age, prevalence of glucose intolerance: 5% and 8% in groups 1 and 2 respectively (not significant). However, group 1 had a higher glucose level 2 h after an oral glucose tolerance test (P < 0.05) and a higher level of HbA1C (P < 0.05) and fructosamine (P = 0.07), concomitant with a lower fasting insulin (P < 0.005), when compared with group 2. Group 2 had a significant increase in both systolic and diastolic blood pressure when compared with group 1 (P < 0.05, P < 0.005 respectively). Group 2 had higher blood pressure levels and higher fasting insulin than group 1, suggesting a relationship between insulin levels and blood pressure in this population.


Synthesis of certain 2-substituted-1H-benzimidazole derivatives as antimicrobial and cytotoxic agents.
A series of 2-substituted-1H-benzimidazole derivatives were synthesized and evaluated for antimicrobial, antifungal and cytotoxic activities. The results showed that all tested compounds showed potent antimicrobial activity against some species of Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi) and fungi (Candida albicans) with minimum inhibitory concentrations (MICs) lower than 0.016 µg/mL. In contrast, all tested compounds were inactive against Staphylococcus aureus (Gram-positive bacterium). The final targets were also tested for their antitumor activity in vitro on cervical carcinoma (HeLa) cell line. Eight of the test compounds displayed more potent cytotoxic effect than doxorubicin at nanomolar concentrations. Compounds 2c and 3c exerted the strongest cytoyoxic effect with IC(50) 15 and 13 nM, respectively.


Smart Fluorescent Probe Strategy for Precision Targeting Hypoxic Tumor.
Both nitroreductase and the folate receptor are highly expressed in hypoxic tumors. The folate receptor is a potential target for tumors, and nitroreductase can selectively turn on the fluorescence of probes by reducing the nitro group to an amino group. Karan et al. (Karana, S., Cho, M., Lee, H., Lee, H., Park, H., Sundararajan, M., Sessler, J., and Hong, K. Near-infrared fluorescent probe activated by nitroreductase for in vitro and in vivo hypoxic tumor detection. J. Med. Chem. 2021) developed a near-infrared fluorescent probe for hypoxia tumor imaging analysis in vitro and in vivo using folate as the targeting site. This promising strategy may promote advances in precision diagnosis and treatment models of malignant tumors. This Viewpoint looks ahead to new possibilities rendered by their studies.


Synthesis and adrenergic properties of new duplicated analogs of methoxamine.
New duplicated analogs of the alpha 1-selective agonist methoxamine and of its cyclic derivative 5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthylamine have been synthesized and tested for their adrenergic properties. All the compounds prepared, presenting a polymethylene spacer of varying length between two units of the active structure, turned out to be completely devoid of any alpha-stimulating activity. Surprisingly, some of them showed a marked beta-adrenergic agonistic effect, being the most interesting compound active at nanomolar concentration.


Factors affecting the visual outcome in acute central serous chorioretinopathy.
To determine the visual outcome in patients with acute Central serous chorioretinopathy (CSCR) and to analyze the association of clinical, angiographic and tomographic factors with final visual outcome in Pakistani population. This study was conducted at AFIO Rawalpindi and PNS Shifa Naval hospital Karachi from November 2011 to August 2016. Fifty five eyes of 53 patients with acute CSCR were included. All patients underwent a detailed ophthalmic examination including SD OCT imaging at baseline, One month and three month and FFA was performed at baseline. Primary outcome measures were measurement of initial and final BCVA and CFT. SPSS 13.0 was used for the analysis of data. Mean age of study population was 36.66 ± 6.24 years. On OCT mean CFT at baseline was 467.49 ± 144.80 µm in affected eye, whereas mean CFT measurements at final follow up was 244.67 ± 32.99 µm (p <0.01). Presenting mean log MAR BCVA was 0.47 ± 0.25 and final mean log MAR BCVA was 0.18 ± 0.14 (p <0.01). Baseline BCVA showed statistically significant association with final BCVA (p=0.03). Presenting VA of 6/12 or better is associated with favorable visual outcome in patients with acute CSCR.


Data-Driven Design of Intelligent Wireless Networks: An Overview and Tutorial.
Data science or "data-driven research" is a research approach that uses real-life data to gain insight about the behavior of systems. It enables the analysis of small, simple as well as large and more complex systems in order to assess whether they function according to the intended design and as seen in simulation. Data science approaches have been successfully applied to analyze networked interactions in several research areas such as large-scale social networks, advanced business and healthcare processes. Wireless networks can exhibit unpredictable interactions between algorithms from multiple protocol layers, interactions between multiple devices, and hardware specific influences. These interactions can lead to a difference between real-world functioning and design time functioning. Data science methods can help to detect the actual behavior and possibly help to correct it. Data science is increasingly used in wireless research. To support data-driven research in wireless networks, this paper illustrates the step-by-step methodology that has to be applied to extract knowledge from raw data traces. To this end, the paper (i) clarifies when, why and how to use data science in wireless network research; (ii) provides a generic framework for applying data science in wireless networks; (iii) gives an overview of existing research papers that utilized data science approaches in wireless networks; (iv) illustrates the overall knowledge discovery process through an extensive example in which device types are identified based on their traffic patterns; (v) provides the reader the necessary datasets and scripts to go through the tutorial steps themselves.


Oxytocin affects the connectivity of the precuneus and the amygdala: a randomized, double-blinded, placebo-controlled neuroimaging trial.
Although oxytocin is one of the most widely studied neuropeptides in recent times, the mechanistic process by which it modulates social-affective behavior in the brain is not yet clearly understood. Thus, to understand the neurophysiological basis of oxytocin effects, we used resting-state functional MRI to examine the effects of intranasal oxytocin on brain connectivity in healthy males. Using a randomized, double-blinded, placebo-controlled, crossover design, 15 healthy male volunteers received 24 IU intranasal oxytocin or placebo prior to resting-state functional MRI acquisition at 3T. We found that oxytocin significantly reduced the degree centrality of the right precuneus (P<.05). Oxytocin also reduced connectivity between the bilateral amygdalae and between the right precuneus and the right and left amygdala (P<.05). Although there were no significant changes in regional homogeneity at the whole brain level, posthoc results showed a reduction involving the right precuneus (P<.05). These results show that oxytocin affects one of the key centers in the brain for social cognition and introspective processing, the precuneus, and enhances our understanding of how oxytocin can modulate brain networks at rest. An improved understanding of the neurophysiological effects of oxytocin can be important in terms of evaluating the mechanisms that are likely to underlie the clinical responses observed upon long-term oxytocin administration.


Genetic counseling and reproductive uncertainty.
Of 836 fertile women seeking genetic counseling, 544 (65%) reported that their major reason for doing so was to obtain information to help in deciding if they should have a child. Thirty-four percent of these 836 women entered counseling uncertain about undertaking a pregnancy in the next 2 years. After counseling, 28% of the 836 had uncertain pregnancy intentions. These included 66% of those who were uncertain and 11% of those who were reproductively certain before counseling. Stepwise logistic regression identified the following as independently and significantly associated with reproductive uncertainty after counseling: 1) uncertainty before counseling; 2) uncertainty about ideal family size; 3) concern about the effects of an affected child on the client's social life; 4) perceived serious problems caring for a child with a birth defect now living at home; and 5) new concerns raised in counseling. Reproductive uncertainty after counseling was not related to characteristics of the risked birth defect, level of risk, treatment potential, or client learning of medical and genetic facts. These data suggest that genetic counseling will not eliminate reproductive uncertainty for many clients, because this uncertainty is related to factors mainly outside the usual scope of counseling.


Recognition of white matter bundles using local and global streamline-based registration and clustering.
Virtual dissection of diffusion MRI tractograms is cumbersome and needs extensive knowledge of white matter anatomy. This virtual dissection often requires several inclusion and exclusion regions-of-interest that make it a process that is very hard to reproduce across experts. Having automated tools that can extract white matter bundles for tract-based studies of large numbers of people is of great interest for neuroscience and neurosurgical planning. The purpose of our proposed method, named RecoBundles, is to segment white matter bundles and make virtual dissection easier to perform. This can help explore large tractograms from multiple persons directly in their native space. RecoBundles leverages latest state-of-the-art streamline-based registration and clustering to recognize and extract bundles using prior bundle models. RecoBundles uses bundle models as shape priors for detecting similar streamlines and bundles in tractograms. RecoBundles is 100% streamline-based, is efficient to work with millions of streamlines and, most importantly, is robust and adaptive to incomplete data and bundles with missing components. It is also robust to pathological brains with tumors and deformations. We evaluated our results using multiple bundles and showed that RecoBundles is in good agreement with the neuroanatomical experts and generally produced more dense bundles. Across all the different experiments reported in this paper, RecoBundles was able to identify the core parts of the bundles, independently from tractography type (deterministic or probabilistic) or size. Thus, RecoBundles can be a valuable method for exploring tractograms and facilitating tractometry studies.


Prediction of late adverse events in pelvic cancer patients receiving definitive radiotherapy using radiation-induced gamma-H2AX foci assay.
Radiation can induce DNA double-stranded breaks, which are typically detected by the fluorescence of phosphorylated histone H2AX. In this study, we examined the usefulness of the dynamics of radiation-induced gamma-H2AX foci of peripheral blood lymphocytes (PBLs), as a marker of DNA repair ability, in predicting late adverse events from radiotherapy. A total of 46 patients with cervical, vaginal and anal canal cancers treated with radical radiotherapy between 2014 and 2019 were included in this analysis. Concurrent chemotherapy was administered in 36 cases (78.3%). Peripheral blood was obtained before treatment, and then irradiated ex vivo with 1 Gy X-ray. The ratio of radiation-induced gamma-H2AX foci in PBLs measured at 30 min and at 4 h was defined as the foci decay ratio (FDR). With a median follow-up of 54 months, 9 patients (19.6%) were observed to have late genitourinary or gastrointestinal (GU/GI) toxicity. The FDR ranged from 0.51 to 0.74 (median 0.59), with a significantly higher incidence of Grade 1 or higher late adverse events in the FDR ≥ 0.59 group. In multivariate analysis, FDR ≥ 0.59 and hypertension also emerged as significant factors associated with the development of late toxicities. Overall, our results suggest that measurement of radiation-induced gamma-H2AX foci in PBLs may predict the risk of late GU/GI toxicities from chemoradiotherapy, which can enable tailoring the radiation dose to minimize adverse effects.


Expression of the PAF receptor in human monocyte-derived macrophages is downregulated by oxidized LDL: relevance to the inflammatory phase of atherogenesis.
Human monocyte-derived macrophages play a major role in the initiation and progression of atherosclerotic lesions as a result of the production of a wide spectrum of proinflammatory and prothrombotic factors. Among such factors is a potent inflammatory phospholipid, platelet-activating factor (PAF), which is produced after macrophage activation. Because the cells involved in PAF biosynthesis are typically targets for the bioactions of PAF via specific cell surface receptors, we evaluated the expression of the PAF receptor in human monocyte-derived macrophages. Oxidized LDL (oxLDL) exerts multiple cellular effects that enhance lesion progression; we therefore investigated the potential modulation of expression of the macrophage PAF receptor by oxLDL. [3H]PAF bound to adherent human macrophages with a K(d) of 2.1 nmol/L and a B(max) of 19 fmol/10(6) cells; approximately 5300 binding sites per cell were detected. OxLDL (100 microg protein per milliliter) induced a twofold decrease in cellular PAF binding after 3 hours at 37 degrees C. Analysis of macrophage mRNA by reverse transcription-polymerase chain reaction (RT-PCR) revealed two forms corresponding to the PAF receptor, of which the leukocyte type (type 1 promoter) predominated. Expression of PAF receptor mRNA, evaluated by quantitative RT-PCR using an actin or a GAPDH mimic, was progressively reduced (up to 70%) by oxLDL up to 6 hours and remained low for at least 24 hours. Such downregulation was reversible after incubation of the cells for 24 hours in oxLDL-free medium. Addition of forskolin (3 micromol/L) or dibutyryl cAMP (1 mmol/L) to macrophage cultures reproduced the oxLDL-mediated inhibition of PAF receptor expression; carbamyl PAF reduced PAF binding and PAF mRNA to a similar degree (approximately 50%). These data demonstrate that atherogenic oxLDL downregulates the expression of both cellular PAF receptors and PAF receptor mRNA in macrophages, consistent with both a diminished bioresponse to PAF and decreased cell motility. Such diminished bioresponse to a powerful antacoid reflects the suppression of an acute inflammatory reaction, thereby leading to chronic, low-level inflammation, such as that characteristic of fatty streaks and more advanced atherosclerotic plaques.


Effects of 3',4'-dihydroxyflavonol on vascular contractions of rat aortic rings.
1. 3',4'-Dihydroxyflavonol (DiOHF) is an effective vasodilator with anti-oxidant activity. The aim of the present study was to elucidate the effects of DiOHF on vascular contractions. 2. Contractile and relaxation responses were determined in rat endothelium-denuded aortic rings mounted in organ baths. In addition, the phosphorylation of myosin light chain (MLC(20)), myosin phosphatase targeting subunit 1 (MYPT1) and protein kinase C (PKC)-potentiated inhibitory protein for heterotrimeric myosin light chain phosphatase of 17 kDa (CPI-17) was determined using western blot analysis. Levels of GTP RhoA, as a marker of RhoA activation, were also measured. 3. Cumulative addition of increasing concentrations of NaF (3.0-12.0 mmol/L) or U46619 (1.0-1000 nmol/L) concentration-dependently increased vascular tension. These responses were inhibited by pretreatment of aortic rings with DiOHF (10, 30 or 100 micromol/L), which dose-dependently decreased vascular contractions induced by 8.0 mmol/L NaF, 30 nmol/L U46619, 0.1 micromol/L phenylephrine and 50 mmol/L KCl. 4. The K(+) channel blockers 4-aminopyridine (3 mmol/L), charybdotoxin (10 nmol/L), apamin (500 nmol/L) and glibenclamide (10 micromol/L) had no effect on vascular relaxation induced by DiOHF (1-30 micromol/L). 5. At 30 micromol/L, DiOHF decreased the activation of RhoA and subsequent phosphorylation of MYPT1, CPI-17 and MLC(20) to almost basal levels. 6. In conclusion, DiOHF decreases vascular contraction at least partly by inhibition of the RhoA/Rho-kinase pathway in rat endothelium-denuded aorta. These results suggest that DiOHF may have therapeutic potential in the treatment of cardiovascular diseases.


The effects of maternal depression on their perception of emotional and behavioral problems of their internationally adopted children.
Even though child psychopathology assessment guidelines emphasize comprehensive multi-method, multimodal, and multi-informant methodologies, maternal-report symptom-rating scales often serve as the predominant source of information. Research has shown that parental mood symptomatology affects their reports of their offspring's psychopathology. For example, the depression-distortion hypothesis suggests that maternal depression promotes a negative bias in mothers' perceptions of their children's behavioral and emotional problems. We investigated this difference of perception between adoptive mothers and internationally adopted children. Most previous studies suffer from the potential bias caused by the fact that parents and children share genetic risks. Data were derived from the Finnish Adoption (FinAdo) survey study (a subsample of adopted children aged between 9 and 12 years, n = 222). The Child Behavior Checklist (CBCL) was used to assess emotional and behavioral problems and competences of the adopted children. The CBCL was filled in by the adopted children and the adoptive mothers, respectively. Maternal depressive symptoms were measured using the short version of the General Health Questionnaire. On average, mothers reported less total CBCL symptoms in their children than the children themselves (0.25 vs 0.38, p-value < 0.01 for difference). Mothers' depressive symptoms moderated the discrepancy in reporting internalizing symptoms (β = - 0.14 and p-value 0.01 for interaction) and the total symptoms scores (β = - 0.22 and p-value < 0.001 for interaction) and externalizing symptoms in girls in the CBCL. The major limitation of our study is its cross-sectional design and the fact that we only collected data in the form of questionnaires. The results of our research support the depression-distortion hypothesis concerning the association of maternal depressive symptoms and child internalizing symptoms and externalizing symptoms in girls in a sample without genetic bias.


Attitudes, Self-Efficacy, and Feasibility: Exploring Social Work Students' Perceptions of Evidence-Based Practice.
The literature on evidence-based practice (EBP) in social work indicates a complex relationship between practitioners' attitudes, views on feasibility, and self-efficacy related to EBP implementation. Qualitative interviews and a self-report questionnaire were completed with 8 social work students. A conceptual framework of their perceptions was developed through thematic analysis. Participants reported mixed EBP attitudes, as both a practice "ideal", but also oppressive, rigid, and dehumanizing. Low confidence regarding research skills affected participants' self-efficacy. Resource constraints impacted feasibility through organizational culture and available practice-relevant research. EBP misconceptions critically impacted educational practices, organizational culture, and practitioners' attitudes. Comprehensive education mindful of professional identity may address misconceptions and enhance self-efficacy. EBP-enabling organizational change and practice-relevant research may alleviate resource constraints. Research should expand on how EBP attitudes and social work identity intersect, the impact of research skills on self-efficacy, and EBP barriers and facilitators in education and organizations.


The Effect of Vitamin D Treatment On Nerve Growth Factor (NGF) Release From Hippocampal Neurons.
Vitamin D, the main function of which is thought to be the maintenance of calcium and phosphate homeostasis and bone structure, has been shown in recent studies to have important roles in brain development as well. A certain vitamin D receptor (VDR) gene haplotype was reported, for the first time by our group, to increase the risk of developing Alzheimer's disease. Our studies also showed that vitamin D prevents beta amyloid-induced calcium elevation and toxicity that target nerve growth factor (NGF) release in cortical neurons; beta amyloid suppresses VDR expression and the disruption of vitamin D-VDR pathway mimics beta amyloid-induced neurodegeneration. In this study, our aim was to investigate the effects of vitamin D on the NGF release from hippocampal neurons. Primary hippocampal neuron cultures that were prepared from 18-day-old Sprague-Dawley rat embryos were treated with vitamin D for 48 hours. The alteration in the NGF release was determined with ELISA. Cytotoxicity tests were also performed for all groups. The NGF release in vitamin D-treated group was significantly higher than in untreated control group. The protective effect of vitamin D against cytotoxicity was also observed. Our results indicated that vitamin D regulates the release of NGF, a very important molecule for neuronal survival of hippocampal neurons as well as cortical neurons.


Interdisciplinary interactive blended learning concept in times of a pandemic - pain medicine "totally digital".
Introduction: Pain medicine is located in different sections of the medical curriculum. In the pandemic situation, an online teaching concept for Q14 which includes several disciplines had to be developed. The goal of the project was to create a fully digitized learning platform for the cross-sectional area Q14 that allows all participating disciplines to address the various learning goals without losing a practical component. Project description: First, the students' expectations regarding education in the field of pain medicine were recorded by means of a survey among medical students. Based on this, a teaching module in a blended learning format was developed, which consisted of two parts. Within a digital learning platform, students were first required to complete consecutive learning units using an interactive learning management system. This was followed by a presence phase (online ZOOM seminar) in which, under the guidance of teaching staff, the therapy suggestions of the individual case studies from the previous learning program were reflected. In the second part, the acquired knowledge was applied to a simulated patient. An evaluation of the online module was carried out through free-text answers and self-assessment of the completion time. The ZOOM seminar was evaluated on the basis of an assessment by the teachers. Results: The survey among students revealed a desire for practical training without "frontal teaching". The resulting project realized this aspect by teaching theory during an online module with case vignettes and interactive learning tasks. The subsequent online presence time during the ZOOM meeting enabled the students to repeat and deepen contents and to ask questions. 170 students completed the entire online program, of which evaluation data were available for 75 students. Self-assessment of completion time averaged at 4-6 hours. In the feedback, 90 aspects were addressed, including mainly comments on content (43%), praise (33%) and comments on technical problems (23%). According to the assessment of the presenters, the students were able to carry out the pain anamnesis survey in a structured manner. The submission of the therapy proposal, however, represents a particular hurdle. Conclusion: With the presented blended learning concept it is possible to address the different learning goals and the interdisciplinarity of Q14 sufficiently. After further processing and improvement of the project, a controlled and more extensive collection of evaluation data is required to further investigate the benefit of the platform for the students regarding achievement of defined learning goals.


Immunocompetent cells producing humoral mediators of bone tissue mineral metabolism during space flight simulation.
During 120-day and 370 day hypokinesia the possibility has been shown of manifestation of mechanism of immunological regulation of osteoclast functions. Supernatants of mononuclear peripheral blood cells which were in vitro nitrogen-stimulated, had an increased potential for resorption in 45Ca-labelled mice fetus long bone organ cultures. Resorbing activity was increased in mononuclear supernatants from some of the subjects exposed to 120-day hypokinesia and from all subjects exposed to 370-day hypokinesia. This variable returned to base-line values after completion of the bed-rest period. Lymphocyte in vitro proliferative activity decreased at the end of hypokinesia and during the initial days of recovery, and the number of active T-rosetting cells was, on the contrary increased. This suggested a possible activation of part of immunocompetent cell population potentially producing humoral regulators of bone cell functions in vivo. A study of a group of healthy males performing their routine daily activity and of patients with local osteoporosis (paradontitis) showed significant differences between normal subjects and patients, confirming the informative value of the method used and allowed to establish approximate limits of physiological variations of the values.


PREVALENCE OF NONTOXIC NODULAR GOITER AFTER A NEARLY TWO-DECADE UNIVERSAL SALT IODIZATION IN A LITTORAL REGION OF SHANDONG PROVINCE, CHINA.
With the introduction of iodized salt, more and more people are exposed to iodine sufficiency in some regions. The purpose of this study was to investigate the prevalence of nontoxic nodular goiter (NTNG) in the littoral region with high iodine supply after a nearly two- decade universal salt iodization. Eight hundred and thirty- five participants (from 25~65 years; males 421 and females 414) were invited for the study from Huan-cui District of Weihai City, Shandong Province from January 2013 to September 2014. All participants were inspected and diagnosed by endocrinologists according to the thyroid function tests and the thyroid gland imaging. After the normal diet of three days, the urine samples of the participants were collected between 8:00AM and 9:00AM and the urinary iodine (UI) concentrations were analyzed using Urinary Iodide Test Kit. The overall prevalence of NTNG in the region was 40.1%, and different prevalence occurred in the different age ranges (p<0.01). The prevalence of NTNG was 32.51%, 37.44%, 49.70%, 58.57 and 74.77% in the age group of ≤ 30, 31-40, 41-50, 51-60 and >60 years, respectively. Meanwhile, the prevalence of NTNG in women (42.08%) was higher than that in men (34.29%, p<0.05). The median of UI concentrations were 139.4μg/L and 101.5μg/L for the group with NTNG and without NTNG, respectively (p<0.01). However, there was no significant difference in UI concentrations among the groups with different age ranges (p>0.05), and statistical difference was not observed for UI concentrations between women and men (p>0.05). Intriguingly, higher UI concentrations were found in the group with larger thyroid size (p<0.01). The iodine excess can lead to the high occurrence of nodular goiter in the littoral region, and individual UI concentration detection is recommended for the iodine nutritional status analysis among normal people when Universal Salt Iodization (USI) continues to be implemented in the region.


Histone acetylation is involved in TCDD‑induced cleft palate formation in fetal mice.
The aim of the present was to evaluate the effects of DNA methylation and histone acetylation on 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD)‑induced cleft palate in fetal mice. Pregnant mice (n=10) were randomly divided into two groups: i) TCDD group, mice were treated with 28 µg/kg TCDD on gestation day (GD) 10 by oral gavage; ii) control group, mice were treated with an equal volume of corn oil. On GD 16.5, the fetal mice were evaluated for the presence of a cleft palate. An additional 36 pregnant mice were divided into the control and TCDD groups, and palate samples were collected on GD 13.5, GD 14.5 and GD 15.5, respectively. Transforming growth factor‑β3 (TGF‑β3) mRNA expression, TGF‑β3 promoter methylation, histone acetyltransferase (HAT) activity and histone H3 (H3) acetylation in the palates were evaluated in the two groups. The incidence of a cleft palate in the TCDD group was 93.55%, and no cases of cleft palate were identified in the control group. On GD 13.5 and GD 14.5, TGF‑β3 mRNA expression, HAT activity and acetylated H3 levels were significantly increased in the TCDD group compared with the control. Methylated bands were not observed in the TCDD or control groups. In conclusion, at the critical period of palate fusion (GD 13.5‑14.5), TCDD significantly increased TGF‑β3 gene expression, HAT activity and H3 acetylation. Therefore, histone acetylation may be involved in TCDD‑induced cleft palate formation in fetal mice.


Is human mating adventitious or the result of lawful choice? A twin study of mate selection.
Pairs of middle-aged twins and their spouses provided data on 74 mainly psychological variables. Neither spousal similarity nor idiosyncratic criteria could account for specific mate selection in these 738 couples. Of the twins (and their spouses), 547 independently rated their initial attraction to their twin's mate (or to their spouse's twin): Findings suggest that characteristics both of the chooser and the chosen constrain mate selection only weakly. This article proposes that it is romantic infatuation that commonly determines the final choice from a broad field of potential eligibles and that this phenomenon is inherently random, in the same sense as is imprinting in precocial birds.


Experiences of Breastfeeding Mothers With Visual Disabilities.
Parents with visual impairment can have difficulty in breastfeeding their babies. This situation may cause mothers to have negative feelings towards the care of their babies and to have problems during breastfeeding process. To examine in detail (1) the breastfeeding experiences of mothers with visual impairment, and (2) the factors that facilitate and prevent these mothers from continuing to breastfeed. This study was a cross-sectional, prospective generic qualitative design. The study sample (N = 15) consisted of mothers with visual impairment aged 18 and over, residing in Turkey, speaking Turkish, having an infant under the age of 2, and with breastfeeding experience. The analysis process was a content analysis approach. Data were collected through video or audio interviews using a semi-structured interview form. Three main themes and 12 subthemes were determined: (1) negative emotions caused by breastfeeding, (2) barriers to initiating and maintaining breastfeeding, and (3) facilitators in initiating and maintaining breastfeeding. The participants in our study stated that health personnel had limited information on how to communicate with and support them. For this reason, it is important that breastfeeding counselors and health care providers receive training about breastfeeding counseling for mothers with visual impairment so that they can provide information and advice to these mothers.


Chemosensory Activation of an Antennular Grooming Behavior in the Spiny Lobster, Panulirus argus, Is Tuned Narrowly to L-Glutamate.
Antennular grooming behavior (AGB) is a stereotyped behavior in crustaceans in which the first pair of antennae, the major olfactory organs, are clasped and wiped repetitively by the third maxillipeds, which also serve as feeding appendages. AGB apparently functions to clear away accumulating debris on or between the antennular aesthetascs (olfactory sensilla). The purpose of this research was to determine whether AGB can be activated by chemicals commonly found in food odors. Lobsters were presented, via headset or handheld pipette, with 27 chemicals found in their food. One chemical, L-glutamate, evoked very high frequencies of wiping. Most chemicals tested were not stimulatory and only a few were weakly stimulatory (adenosine-5'-monophosphate, glycine, D-glutamate). This is surprising because previous studies have shown that other behaviors (antennular flick, search) can be evoked by a much broader array of chemicals found in food odorants. On the basis of these results, we propose that chemosensory neurons that specifically detect L-Glu activate AGB through a recently described non-olfactory pathway. Furthermore, we propose that the role of L-Glu in evoking AGB is based on its electrostatic properties. Because it has a high probability of electrostatic adherence to the antennular cuticle, L-Glu is a sensitive indicator of fouling by food-associated chemicals and thus an appropriate compound to stimulate antennular grooming.


[Morphological diagnosis of pseudocystic tumors of the liver].
Ten cases of pseudocystic hepatic tumors were observed during the past ten years. This entity is very rare in comparison with benign hepatic cysts. Careful analysis of the characteristics of these lesions usually allows to differentiate them from benign cysts. Of importance are wall thickness, mural nodules and fluid/fluid levels on ultrasound and/or computed tomography scanning. In our series, sonography depicted the true morphology of these cystic masses more clearly than computed tomography. If definitive diagnosis cannot be made by morphologic examinations, percutaneous aspiration of the cystic lesion, a simple and safe method, should be considered.


Impact of a nurse led telephone intervention on satisfaction and health outcomes of children with inflammatory rheumatic diseases and their families: a crossover randomized clinical trial.
Children suffering from rheumatic disease are faced with multidimensional challenges that affect their quality of life and family dynamics. Symptom management and monitoring of the course of the disease over time are important to minimize disability and pain. Poor disease control and anticipation of the need for treatment changes may be prompted by specialist medical follow-up and regular nurse-led consultations with the patient and families, in which information and support is provided. The purpose of this study was to evaluate the impact of a nurse-led telephone intervention or Telenursing (TN) compared to standard care (SC) on satisfaction and health outcomes of children with inflammatory rheumatic diseases and their parents. A multicentered, randomized, longitudinal, crossover trial was conducted with pediatrics outpatients newly diagnosed with inflammatory rheumatic diseases. Participants were randomly assigned to two groups TN and SC for 12 months and crossed-over for the following 12 months. TN consisted of providing individualized affective support, health information and aid to decision making. Satisfaction (primary outcome) and health outcomes were assessed with the Client Satisfaction Questionnaire-8 and the Juvenile Arthritis Multidimensional Assessment Report, respectively. A mixed effect model, including a group x time interaction, was performed for each outcome. Satisfaction was significantly higher when receiving TN (OR = 7.7, 95% CI: 1.8-33.6). Morning stiffness (OR = 3.2, 95% CI: 0.97-7.15) and pain (OR = 2.64, 95% CI: 0.97-7.15) were lower in the TN group. For both outcomes a carry-over effect was observed with a higher impact of TN during the 12 first months of the study. The other outcomes did not show any significant improvements between groups. TN had a positive impact on satisfaction and on morning stiffness and pain of children with inflammatory rheumatic diseases and their families. This highlights the importance of support by specialist nurses in improving satisfaction and symptom management for children with inflammatory rheumatisms and their families. ClinicalTrial.gov identifier: NCT01511341 (December 1st, 2012).


Cooperative effect of calcium binding to adjacent troponin molecules on the thin filament-myosin subfragment 1 MgATPase rate.
The myosin subfragment 1 (S1) MgATPase rate was measured using thin filaments with known extents of Ca2+ binding controlled by varying the ratio of native cardiac troponin versus an inhibitory troponin with a mutation in the sole regulatory Ca2+ binding site of troponin C. Fractional MgATPase activation was less than the fraction of troponins that bound Ca2+, implying a cooperative effect of bound Ca2+ on cross-bridge cycling. Addition of phalloidin did not alter cooperative effects between bound Ca2+ molecules in the presence or absence of myosin S1. When the myosin S1 concentration was raised sufficiently to introduce cooperative myosin-myosin effects, lower Ca2+ concentrations were needed to activate the MgATPase rate. MgATPase activation remained less than Ca2+ binding, implying a true, not just an apparent, increase in Ca2+ affinity. MgATPase activation by Ca2+ was more cooperative than could be explained by cooperativeness of overall Ca2+ binding, the discrepancy between Ca2+ binding and MgATPase activation, or interactions between myosins. The results suggest the thin filament-myosin S1 MgATPase cycle requires calcium binding to adjacent troponin molecules and that this binding is cooperatively promoted by a single cycling cross-bridge. This mechanism is a potential explanation for Ca2+-mediated regulation of cross-bridge kinetics in muscle fibers.


SIRT1 Inhibits Apoptosis by Promoting Autophagic Flux in Human Nucleus Pulposus Cells in the Key Stage of Degeneration via ERK Signal Pathway.
The application of biomolecular interventions in the early stage of intervertebral disc degeneration (IVDD) is considered an ideal method for the treatment of IVDD. However, the precise definition of the "early stage" of IVDD is unclear. Silent information regulation 2 homologue-1 (SIRT1) can protect human degenerative nucleus pulposus (NP) cells from apoptosis by activating autophagy. However, the mechanism of this effect is still unclear. This study tried to confirm the "early stage" of IVDD and the role of NP cell autophagy during IVDD as well as to determine the mechanism by which SIRT1 protects NP cells. The characteristics of the NP in various stages of degeneration were assessed to confirm the "early stage" of IVDD. Then, autophagy and apoptosis were detected in NP cells after SIRT1 upregulation/downregulation. Finally, LY294002 and PD98059 were used to inhibit the AKT/ERK pathway to determine the mechanism by which SIRT1 regulates autophagy in NP cells. Our data showed that mildly degenerative (Pfirrmann grade III with normal height of intervertebral disc) NP cells may be the key target for biomolecular interventions in IVDD and that SIRT1 protects human mildly degenerative NP cells from apoptosis by activating autophagy via the ERK signalling pathway. Our data showed that SIRT1 inhibits apoptosis by promoting the autophagic flux in NP cells via the ERK signalling pathway during the key stage of degeneration. These findings will assist in the development of novel therapeutic approaches for IVDD treatment.


NIST Calibration of a Neutron Spectrometer ROSPEC.
A neutron spectrometer was acquired for use in the measurement of National Institute of Standards and Technology neutron fields. The spectrometer included options for the measurement of low and high energy neutrons, for a total measurement range from 0.01 eV up to 17 MeV. The spectrometer was evaluated in calibration fields and was used to determine the neutron spectrum of an Americium-Beryllium neutron source. The calibration fields used included bare and moderated (252)Cf, monoenergetic neutron fields of 2.5 MeV and 14 MeV, and a thermal-neutron beam. Using the calibration values determined in this exercise, the spectrometer gives a good approximation of the neutron spectrum, and excellent values for neutron fluence, for all NIST calibration fields. The spectrometer also measured an Americium-Beryllium neutron field in a NIST exposure facility and determined the field quite well. The spectrometer measured scattering effects in neutron spectra which previously could be determined only by calculation or integral measurements.


IXL, a new subunit of the mammalian Mediator complex, functions as a transcriptional suppressor.
Transcription factors play an essential role in altering gene expression. Much progress about transcription factors has been made toward the understanding of normal physiological processes, embryonic development, and human diseases. In the present study, we report the identification and characterization of a novel human gene, (Drosophila) intersex-like (IXL), from a human embryonic heart cDNA library. IXL encodes a putative protein of 221 amino acids. The protein is conserved across different species during evolution. Northern blot analysis indicates that IXL is expressed in various tissues of human adult and during three different developmental stages of embryo. In COS-7 cells, IXL protein is localized to nucleus and cytoplasm. IXL is a transcription suppressor when fused to Gal-4 DNA-binding domain and cotransfected with VP-16. Overexpression of IXL in COS-7 cells inhibits the transcriptional activities of SRE and AP-1, suggesting that the IXL protein may act as a transcriptional suppressor in mitogen-activated protein kinase signaling pathway to mediate cellular functions.


Epidermal growth factor induces internalization but not degradation of the epidermal growth factor receptor in a human breast cancer cell line.
Metabolism of the epidermal growth factor (EGF) receptor was studied in the MDA-MB-231 human breast cancer cell line. As in normal fibroblasts the EGF receptor from MDA-MB-231 cells was synthesized from a Mr = 160,000 precursor and tunicamycin treatment of cells resulted in accumulation of a Mr = 130,000 polypeptide. Unlike normal fibroblasts in which a Mr = 170,000 mature form of the EGF receptor was found, MDA-MB-231 cells contained a Mr = 172,000 mature form. Addition of EGF to MDA-MB-231 cells led to rapid internalization of EGF receptors, however, internalization did not affect receptor half-life and receptors did not recycle to the cell surface. EGF receptors could be visualized by immunofluorescence and remained sequestered in intracellular membranous structures following internalization. EGF was degraded slowly by MDA-MB-231 cells relative to degradation of EGF by normal cells. A high endogenous level of in vivo phosphorylation of threonine 654 of the EGF receptor was found in MDA-MB-231 cells and treatment of cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) further stimulated phosphorylation of this residue. EGF induced receptor internalization resulted in dephosphorylation of threonine 654. The significance of these unusual properties of EGF receptor metabolism in MDA-MB-231 cells is discussed.


Electronic collimation of radiographic images: does it comprise an overexposure risk?
To investigate whether electronic collimation software, which is available in all digital X-ray systems, may comprise an overexposure risk. In the context of surveys on Diagnostic Reference Levels carried out in two radiographic facilities, along with data on exposure factors, the radiographic field sizes were also recorded. In one facility (Unit A), a wireless flat panel detector is used with a conventional X-ray unit, while in the other, a fully digital system is installed (Unit B). The electronically collimated image sizes were compared with the original radiation field sizes. The differences between these two systems concerning the field sizes and the mode of electronic collimation utilization were investigated. In Unit A, manual electronic collimation was extensively used and cases where the radiation field size was up to three times larger than that electronically collimated, were identified. On the contrary, in Unit B radiation fields were smaller and electronic collimation was automatic. When electronic collimation is used in manual mode instead of proper pre-exposure collimation, then it does comprise an overexposure risk. The risk is larger in radiographic units where the field size is not automatically selected according to the examination protocol and no interlocks against oversized collimation settings exist. Advances in knowledge: When radiologists review masked images to make the diagnosis, possible suboptimal X-ray field collimation practices may go unnoticed for long. Therefore, radiologists and medical physicists should periodically survey the original images to determine the actual radiation field sizes used for each radiographic examination type.


Development of a rabbit corneal equivalent using an acellular corneal matrix of a porcine substrate.
The tissue equivalent that mimics the structure and function of normal tissue is a major bioengineering challenge. Tissue engineered replacement of diseased or damaged tissue has become a reality for some types of tissue such as skin and cartilage. The tissue engineered corneal epithelium, stroma, and endothelium scaffold are promising concepts in overcoming the current limitations of a cornea replacement with an allograft. The acellular corneal matrix from porcine (ACMP) was examined as a potential corneal cell sheet frame. The physical and mechanical properties of strength, expansion, transparency, and water content of the ACMP were measured. The major antigens of the cell components were completely removed with series of extraction methods, the major antigens of the cell components were identified by hematoxylin and eosin (HE), immunofluorescence staining, and scanning electron microscopy. The structural properties were investigated by HE stain and scanning electron microscopy. The three types of rabbit corneal cells were cultured in vitro, and characteristics were investigated by colony formation efficiency (CFE), BrdU staining, immunofluorescence staining, and western blot assay of keratin 3 (K3), vimentin, and aquaporin A. The biocompatibility of the ACMP was investigated for one month using rabbit corneal stroma and three types of cultured corneal cells both in vivo and in vitro. The three types of cultured rabbit corneal cells were seeded onto ACMP of each side at a cell density of 5.0 x 10(3) cells/mm(2). The optical and mechanical properties of the ACMP were similar to the normal porcine cornea. The collagen fiber interconnected to the network, formed regular collagen bundles of the ACMP, and was parallel to the corneal surface. The ACMP was transferred to the rabbit cornea stroma, which showed an intact epithelium and keratocytes in the implant region. There were no inflamed cells or new vessel invasion one month after transplantation. The three types of cultured rabbit corneal cells were positive for K3, vimentin, and aquaporin A. CFE and BrdU (5-bromo-2'-deoxyuridine) staining showed no statistical difference. The cultured rabbit corneal limbal epithelial cells, keratocyte cells, and endothelial cells formed a confluent cell sheet on the ACMP, which consisted of one to two cell layers. Immunofluorescence and scanning electron microscopy examination showed that the cells steadily adhered to the surface of the ACMP and maintained their conformation and special molecule expression such as K3, vimentin, and aquaporin A. Rabbit corneal epithelium-ACMP, keratocytes-ACMP, and endothelium-ACMP scaffold was built in vitro. The rabbit corneal scaffold was made by the ACMP as a frame with three types of allogeneic rabbit corneal cells. This is a new concept in treating injured corneas.


[Prevalence of obesity in school children in Ivory Coast].
According to the World Health Organization, an increased prevalence of hypertension in children is observed since several years due to an epidemic of childhood obesity. What is the extent of this epidemic in our African context? We conducted a prospective descriptive study of pupils encountered in primary and secondary schools of the district of Abidjan from May 3 to June 1st 2010. A sample of 2038 pupils aged 6 to 18 years was randomly selected. Overweight in pupils was assessed by body mass index (BMI). There were 1182 girls (58%) and 856 boys (42%) whose average age was 12.7±3.6 years. The average weight was 42.6kg±16 (range 14.6 to 106.2kg), the average size was 1.48m±0.19 (range 1 to 1.95m). BMI was 17.2kg/m(2)±3.7 (range 14.6-35.7). The prevalence of obesity was of 5%. In addition, 4% of the students were overweight, 39% extremely thin, 25% thin and 27% normal. Obesity was more common in girls (6.8%) than boys (1.8%). The prevalence of obesity in hypertensives was 16%. BMI influenced the systolic and diastolic blood pressure in both sexes (P<0.001 in both cases). Childhood obesity exists in a country like the Ivory Coast where wealthness is far from generalized. A well-organized management of childhood obesity is necessary to avoid complications such as hypertension.


Errors of parameters of distribution functions for spherical bodies stochastically estimated on a random test plane.
The parameters of some distribution functions for the radius of spherical bodies randomly dispersed in a three-dimensional space can be estimated on a random test plane of unit surface area. In this estimation the set of measured Nao, delta and (delta2) or that of Nlambdao, lambda and (lambda2) is used. They are number of circles, arithmetical mean and secondary moment of circle diameters or number of chords delivered by intersection of a test line of unit length with circles, arithmetical mean and secondary moment of chord length, respectively. Provided that the region of measurement is sufficiently large, intraregional errors of these quantities expressed as the squares of coefficient of variation C are approximately: [C(Nao)]omega2=1/Nao, [C(delta)omega2=(32/3pi2)(Q3/Q2(2))(1/Nao) and [C(delta2)]omega2=(6/5)(Q5/Q3(2))(1/Nao); [C(Nlambdao)]omega2=1/MNlambdao, [C(lambda)]omega2=(9/8)(Q4Q2/Q3(2))(1/MNlambdao) and [C(lambda2)]omega2=(4/3)(Q6Q2/Q4(2))(1/MNlambdao). In these expressions Qn is a quotient defined by (Dn)/Dn, D and n being sphere diameter and a positive integer, respectively. The first three expressions may be used in these forms as the errors for the total region containing spheres. In the second three expressions M is the number of random test lines of unit length. When M is small, they can stand for the errors of the total region. In the case of large M, however, interregional errors or errors of sampling have to be added to them. The geometrical parameter of a distribution function of D is estimated from (delta2)/delta2 or (lambda2)/lambda2. The error of this ratio W is given by: [C(W)]2=[C(X2)-2C(X)]2, where X stands for delta or lambda.


[ Intermittent, longterm polychemotherapy in combination with radical operation of bronchial carcinoma (author's transl)].
A preliminary evaluation of a randomized, prospective clinical study of combined polychemotherapy in bronchial carcinoma is presented. The comparison of survival-curves shows a positive tendency in favor of the treatment and justifies the continuation and extension of the study. The data presented are based on the findings of 106 patients who underwent radical surgical operations due to bronchial carcinoma and of 114 patients as a comparison who in addition received aftertreatment with high doses of cytostatics applied intermittently. The importance of the influence of the clinical symptoms on the prognosis and on the effect of the Chemotherapy is emphasized.


[Simultaneous determination of three benzimidazole fungicides in fruits and vegetables by capillary electrophoresis based on bacterial cellulose].
A simple and rapid capillary electrophoresis (CE) method was developed for the determination of trace thiophanate-methyl, carbendazim and benomyl in fruits and vegetables. Herein, bacterial cellulose (BC) was used as additive in running buffer to improve the separation efficiency. CE experimental parameters such as detection wavelength, concentration and pH of the running buffer, separation voltage as well as the contents of BC in running buffer were systematically investigated. Under the optimized conditions, three benzimidazole fungicides could be accurate quantified in 8 min using H3BO3/Na2B4O7 (4 mmol/L, pH 9.0) containing 0.3% (mass fraction) BC for background electrolyte, 15 kV for the separation voltage, 25℃ for the column temperature and 275 nm for detection wavelength. Good linearities for the three benzimidazole fungicides were obtained with correlation coefficients (r2) ≥ 0.997. The limits of detection (LODs) of the three benzimidazole fungicides were between 5.0 and 10.0 μg/L. The relative standard deviations (RSDs, n=5) of inter-day were 0.82%-1.0% for retention times and 2.4%-2.9% for peak areas. The proposed method was further applied to determine the residues of the three benzimidazole fungicides in fruits and vegetables. The recoveries were in the range of 93.5%-103.0% with RSDs no more than 8.0%. These results indicated that the proposed method can serve as an efficient tool for the simultaneous determination of the three benzimidazole fungicides in fruits and vegetables.


The vertically integrated pharmacy department.
Pharmacy's challenges and opportunities during a transition from a traditional hospital to an integrated health system are discussed with reference to the experience of a medical center in Vancouver, Washington. When a traditional hospital makes the transition to an integrated health system, pharmacy directors must consider how the core business will be affected, how pharmacy can add value, and how to best apply the skills of the pharmacy department. A well-trained staff that shares a view of the new organization and that can think outside the traditional hospital paradigm is required. New health systems will focus on quality-related outcomes at low cost and on disease management. Partnerships between providers and health care staff will be beneficial. To compete for capitated contracts, health systems will need to deliver services other than acute care to a broad geographic area, and primary care will be more prominent. There will be a shift toward outpatient services, and pharmacy departments will be under increasing pressure to develop outpatient pharmaceutical services. Pharmacy departments will also need to develop treatment guidelines for outpatients and to better manage drug costs by working with new business clients, improving continuity of care, increasing patients' access to care, having pharmacists provide hospice care, and implementing remote prescription-order entry. New health systems will need to have a clear understanding of how their core business is changing; the organizational strategy of a health system must include effective communication of change to staff members with the goal of overcoming traditional thinking.


Interactions of palmitoyl carnitine with the endothelium in rat aorta.
1. Palmitoyl carnitine (10-1000 microM) resembled Bay K 8644 (10-1000 nM) in that it directly contracted rat aortic rings which were partially depolarized with K+ (12 mM). However, the effects of Bay K 8644 were reduced in the presence of endothelium whereas the presence of the endothelium hardly affected the palmitoyl carnitine-induced contractions, which occurred at high concentrations (greater than 10 microM). 2. Lower concentrations of palmitoyl carnitine (0.3-30 microM; EC50 1.1 microM), but not Bay K 8644, carnitine or palmitic acid, antagonized the relaxant effects of acetylcholine in rat aorta. The antagonism was specific for endothelium-dependent relaxations, in that the relaxations to ATP and the calcium ionophore A23187 were also non-competitively antagonized, albeit at slightly higher concentrations, whereas the direct relaxant effects of sodium nitroprusside were unaffected. Palmitoyl carnitine therefore antagonizes the effects or the release of endothelial-derived relaxant factor (EDRF). The inhibitory effects were reversed on prolonged washout, indicating that the effects were not due to destruction of the endothelial cells. 3. In superfusion experiments, palmitoyl carnitine inhibited the release of EDRF from rat aorta but did not affect the responsiveness to exogenous EDRF, indicating a site of action at the endothelial cell. In superfusion experiments, palmitoyl carnitine, and lysophosphatidyl choline, caused direct relaxations of the aorta, indicating EDRF release, prior to inhibition of release evoked by receptor stimulation. These substances may modulate vascular responsiveness under certain conditions.


Cholinesterase activity in some human lymphatic organs.
(1) Cholinesterase activity was investigated in some human lymphatic organs (palatine tonsil, 'normal' spleen, 'bilharzial' spleen, thymus, lymph node and appendix) using GOMORI'S modification of KOELLE and FRIEDENWALD'S thiocholine iodide method, hydrolyzing acetylthiocholine iodide and butyrylthiocholine iodide. (a) Acetyl- and butyrylcholinesterases seemed to be different enzymes; but when they have the same pattern of activity, the latter generally offers a weaker reaction. (b) All the lymphatic follicles of the tonsil, those found in the cortex of the cervical lymph nodes as well as those present in the appendix, were stainable with both acetyl- and butyrylcholinesterase. (c) Acetylcholinesterase activity was not demonstrated in the Malpighian bodies of the 'normal' spleen, but the reaction was strongly present in the blood vessels (including the central arterioles) as well as in the capsule and the different components of the trabecular system. (d) In 'bilharzial' splenomegaly a relatively strong activity started to appear in the Malpighian corpuscles, manifested as a brownish precipitate in their centres. Also some patchy positive areas began to make their appearance in the tissue of the red pulp and had a particular arrangement around the Malpighian corpuscules, in such a way as to 'wall them off' from the tissue of the red pulp. (e) In the thymus no acetylcholinesterase activity was encountered, except in Hassal's corpuscles and in the trabeculae between the thymic lobules. (2) The data obtained in this work were discussed in relation to previous works in other laboratories and it seems that a species difference exists. (3) Cholinesterases may be present in the lymphatic tissue in order to get rid of some potentially toxic esters resulting from the necrobiotic phenomena accompanying the high mitotic activity found especially in the germinal centres of the lymphoid follicles. (4) There are many unanswered questions about the coexistence of the phosphatases and cholinesterases in the same places; their concomitant association in the lymphatic tissue may represent a special case within the framework of a more general mechanism.


Aliphatic polycarbonates based on carbon dioxide, furfuryl glycidyl ether, and glycidyl methyl ether: reversible functionalization and cross-linking.
Well-defined poly((furfuryl glycidyl ether)-co-(glycidyl methyl ether) carbonate) (P((FGE-co-GME)C)) copolymers with varying furfuryl glycidyl ether (FGE) content in the range of 26% to 100% are prepared directly from CO2 and the respective epoxides in a solvent-free synthesis. All materials are characterized by size-exclusion chromatography (SEC), (1)H NMR spectroscopy, and differential scanning calorimetry (DSC). The furfuryl-functional samples exhibit monomodal molecular weight distributions with Mw/Mn in the range of 1.16 to 1.43 and molecular weights (Mn) between 2300 and 4300 g mol(-1). Thermal properties reflect the amorphous structure of the polymers. Both post-functionalization and cross-linking are performed via Diels-Alder chemistry using maleimide derivatives, leading to reversible network formation. This transformation is shown to be thermally reversible at 110 °C.


Design and Construction of Vibrio cholerae Strains That Harbor Various CTX Prophage Arrays.
Toxigenic Vibrio cholerae strains arise upon infection and integration of the lysogenic cholera toxin phage, the CTX phage, into bacterial chromosomes. The V. cholerae serogroup O1 strains identified to date can be broadly categorized into three main groups: the classical biotype strains, which harbor CTX-cla; the prototype El Tor strains (Wave 1 strains), which harbor CTX-1; and the atypical El Tor strains, which harbor CTX-2 (Wave 2 strains) or CTX-3~6 (Wave 3 strains). The efficiencies of replication and transmission of CTX phages are similar, suggesting the possibility of existence of more diverse bacterial strains harboring various CTX phages and their arrays in nature. In this study, a set of V. cholerae strains was constructed by the chromosomal integration of CTX phages into strains that already harbored CTX phages or those that did not harbor any CTX phage or RS1 element. Strains containing repeats of the same kind of CTX phage, strains containing the same kind of CTX phage in each chromosome, strains containing alternative CTX phages in one chromosome, or containing different CTX phages in each chromosome have been constructed. Thus, strains with any CTX array can be designed and constructed. Moreover, the strains described in this study contained the toxT-139F allele, which enhances the expression of TcpA and cholera toxin. These characteristics are considered to be important for cholera vaccine development. Once their capacity to provoke immunity in human against V. cholerae infection is evaluated, some of the generated strains could be developed further to yield cholera vaccine strains.


Scanning electron microscopy of cornea re-epithelization after transplanted with bilayered corneal construct.
The present work was to determine the development and re-epithelization of bilayered corneal construct (BCC) in vitro and in vivo using scanning electron microscopy (SEM). The in vitro BCC was transplanted to the rabbit's eye and after 90 days the BCC was harvested and analyzed. The corneas were processed for morphology studies. The result indicates that the BICC that was transplanted for 90 days showed good development and re-epithelization of epithelial layer similar to the normal cornea.


EVALUATION OF THE RESTRICTED MAXIMUM-LIKELIHOOD METHOD FOR ESTIMATING PHYLOGENETIC TREES USING SIMULATED ALLELE-FREQUENCY DATA.
Comparisons are made of the accuracy of the restricted maximum-likelihood, Wagner parsimony, and UPGMA (unweighted pair-group method using arithmetic averages) clustering methods to estimate phylogenetic trees. Data matrices were generated by constructing simulated stochastic evolution in a multidimensional gene-frequency space using a simple genetic-drift model (Brownian-motion, random-walk) with constant rates of divergence in all lineages. Ten differentphylogenetic tree topologies of 20 operational taxonomic units (OTU's), representing a range of tree shapes, were used. Felsenstein's restricted maximum-likelihood method, Wagner parsimony, and UPGMA clustering were used to construct trees from the resulting data matrices. The computations for the restricted maximum-likelihood method were performed on a Cray-1 supercomputer since the required calculations (especially when optimized for the vector hardware) are performed substantially faster than on more conventional computing systems. The overall level of accuracy of tree reconstruction depends on the topology of the true phylogenetic tree. The UPGMA clustering method, especially when genetic-distance coefficients are used, gives the most accurate estimates of the true phylogeny (for our model with constant evolutionary rates). For large numbers of loci, all methods give similar results, but trends in the results imply that the restricted maximum-likelihood method would produce the most accurate trees if sample sizes were large enough.


Falling films and the Marangoni effect.
The instability of a falling liquid film of an aqueous surfactant solution along a vertical slope with surfactant adsorption-desorption at its open surface originating surface stresses (Marangoni effect) is investigated. The diffusion of surfactant to the film surface from the bulk and desorption of surfactant to the gas phase are taken into account. The Navier-Stokes and Fick equations are reduced to a system of simpler hence, analytically and numerically, more tractable nonlinear evolution equations albeit with nine dimensionless parameters. The linear stability analysis yields a dispersion equation that is numerically solved and eigenvalues are obtained for various values of significant dimensionless parameters. A very rich picture of instabilities appears. In addition to the earlier known (Kapitza) hydrodynamic mode there are up to four new (Marangoni-driven) diffusion modes. Two modes travel with the liquid velocity on the film surface and the other two travel on their own downstream and upstream, respectively. One diffusion mode could be identified, in the reference frame moving with the liquid on the film surface, as a monotonic instability mode hence leading to a patterned film surface. All other modes are oscillatory ones. Resonance of modes is also predicted for suitable combinations of the parameters of the problem. The mode observed depends upon the surface stress (in terms of a dimensionless Marangoni number), the particular choice of the adsorption-desorption kinetics, and the surface tension state equation at the open surface of the film.


Landscape of genomic alterations in cervical carcinomas.
Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide. The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established. Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as several copy-number alterations in the pathogenesis of cervical carcinomas. Here we report whole-exome sequencing analysis of 115 cervical carcinoma-normal paired samples, transcriptome sequencing of 79 cases and whole-genome sequencing of 14 tumour-normal pairs. Previously unknown somatic mutations in 79 primary squamous cell carcinomas include recurrent E322K substitutions in the MAPK1 gene (8%), inactivating mutations in the HLA-B gene (9%), and mutations in EP300 (16%), FBXW7 (15%), NFE2L2 (4%), TP53 (5%) and ERBB2 (6%). We also observe somatic ELF3 (13%) and CBFB (8%) mutations in 24 adenocarcinomas. Squamous cell carcinomas have higher frequencies of somatic nucleotide substitutions occurring at cytosines preceded by thymines (Tp*C sites) than adenocarcinomas. Gene expression levels at HPV integration sites were statistically significantly higher in tumours with HPV integration compared with expression of the same genes in tumours without viral integration at the same site. These data demonstrate several recurrent genomic alterations in cervical carcinomas that suggest new strategies to combat this disease.