Detection of Highway Pavement Damage Based on a CNN Using Grayscale and HOG Features.
Aiming at the demand for rapid detection of highway pavement damage, many deep learning methods based on convolutional neural networks (CNNs) have been developed. However, CNN methods with raw image data require a high-performance hardware configuration and cost machine time. To reduce machine time and to apply the detection methods in common scenarios, the CNN structure with preprocessed image data needs to be simplified. In this work, a detection method based on a CNN and the combination of the grayscale and histogram of oriented gradients (HOG) features is proposed. First, the Gamma correction was employed to highlight the grayscale distribution of the damage area, which compresses the space of normal pavement. The preprocessed image was then divided into several unit cells, whose grayscale and HOG were calculated, respectively. The grayscale and HOG of each unit cell were combined to construct the grayscale-weighted HOG (GHOG) feature patterns. These feature patterns were input to the CNN with a specific structure and parameters. The trained indices suggested that the performance of the GHOG-based method was significantly improved, compared with the traditional HOG-based method. Furthermore, the GHOG-feature-based CNN technique exhibited flexibility and effectiveness under the same accuracy, in comparison to those deep learning techniques that directly deal with raw data. Since the grayscale has a definite physical meaning, the present detection method possesses a potential application for the further detection of damage details in the future.


The tilt after-effect: changes with stimulus size and eccentricity.
Previous evidence that the tilt after-effect (TAE) is larger when the stimuli are viewed peripherally rather than centrally was confirmed. An increase in viewing distance also increased TAE size. However, the increase in the TAE in peripheral vision was abolished if stimuli were increased in size to compensate for the change in the cortical magnification factor. Both the decrease in field diameter and increase in spatial frequency with viewing distance were found to influence the size of the TAE. When the data were expressed in cortical terms, the TAE was found to increase with spatial frequency, and decrease with field diameter, regardless of retinal position. The functional significance of these effects is discussed.


Left main coronary artery obstruction. Follow-up of thirty patients with and without surgery.
Thirty patients, 20 males and 10 females, having a 50% or greater obstruction of the left main coronary artery, were evaluated. Their ages ranged from 40 to 71 years (mean 53.8 years). All patients had angina pectoris, the duration of which varied from 2 months to 20 years (mean 5.4 years). Twenty-four patients (80%) had accelerated angina pectoris; 17 (56.7%) had prior myocardial infarction, and 27 (90%) were found to have coexisting three-vessel disease and abnormal left ventricular contraction. There were no deaths or serious arrhythmias related to cardiac catheterization procedures. In the 11 unoperated patients 5 (45%) died within the first year of follow-up; however, all except one death occurred in patients with diffuse distal coronary artery disease technically unsuitable for surgery. Among the six survivors four were considered surgical candidates. These four patients have continued to have symptoms of angina pectoris with a mean follow-up period of 17.5 months (16 to 20 months). In the 19 patients who underwent aortocoronary saphenous vein bypass grafting, there was one immediate postoperative death (surgical mortality 5.3%) and one late death. The 17 survivors in the surgical group have a mean follow-up period of 17.3 months (8 to 31 months); 13 of them have clinically improved with 6 being totally free of angina pectoris. Thus, mortality is extremely high in those with poor distal vasculature technically unsuitable for surgery, but mortality is relatively low in patients who have technically bypassable lesions whether treated surgically or medically. Although saphenous vein bypass grafting appears to be more effective in providing clinical improvement, asymptomatic left main coronary obstruction may not justify surgical therapy.


Susceptibility of skeletal muscle to Coxsackie A2 virus infection: effects of botulinum toxin and denervation.
Coxsackie A viruses can infect denervated but not innervated mature skeletal muscles. The role of synaptic transmission in preventing susceptibility to Coxsackievirus infection was studied by surgically denervating leg muscles of mice or injecting the muscles with botulinum toxin to block quantal release of acetylcholine. Control muscles were injected with heat-inactivated toxin. Subsequent injection of Coxsackie A2 virus resulted in extensive virus replication and tissue destruction in the denervated and botulinum toxin-treated muscles, while the control muscles showed only minimal changes. This suggests that the susceptibility of skeletal muscle to Coxsackievirus infection is regulated by synaptic transmission.


New clues to understanding HIV nonprogressors: low cholesterol blocks HIV trans infection.
A small percentage of HIV-infected subjects (2 to 15%) are able to control disease progression for many years without antiretroviral therapy. Years of intense studies of virologic and immunologic mechanisms of disease control in such individuals yielded a number of possible host genes that could be responsible for the preservation of immune functions, from immune surveillance genes, chemokines, or their receptors to anti-HIV restriction factors. A recent mBio paper by Rappocciolo et al. (G. Rappocciolo, M. Jais, P. Piazza, T. A. Reinhart, S. J. Berendam, L. Garcia-Exposito, P. Gupta, and C. R. Rinaldo, mBio 5:e01031-13, 2014) describes another potential factor controlling disease progression: cholesterol levels in antigen-presenting cells. In this commentary, we provide a brief background of the role of cholesterol in HIV infection, discuss the results of the study by Rappocciolo et al., and present the implications of their findings.


T and B lymphocyte levels in the peripheral blood of dogs affected with cyclic neutropenia.
Canine cyclic neutropenia (CN), a heritable disease of Collie dogs, is characterized by the periodic cycling of formed elements of blood and the near disappearance of neutrophils every 11-12 days. Studies suggest that lymphocyte activity and regulatory mechanisms may be abnormal in CN. In this study, an immunofluorescence in the peripheral blood of normal CN Collies. Normal Collie dogs (N = 10) had 73.0 +/- 2.4% T-lymphocytes, whereas CN dogs (N = 4) had only 63.2 +/- 1.9% similar cells among peripheral blood lymphocytes (P less than 0.005). Studies on B-lymphocytes showed that normal Collie dogs (N = 10) had 17.8 +/- 2.0%, whereas CN dogs (N = 4) had 29.6 +/- 3.3% B-lymphocytes (P less than 0.005). Absolute counts for B-lymphocyte levels for 2 CN Collie dogs (N = 10) had 17.8 +/- 2.0%, whereas CN dogs (N = 4) had 29.6 +/- 3.3% B-lymphocytes (P less than 0.005). Absolute counts for B-lymphocytes were also increased in CN dogs. In a related study, daily changes in T- and B-lymphocyte levels for 2 CN Collies and 1 age-and-sex matched normal Collie were monitored over the course of a 2-week hematopoietic cycle. Similar differences in peripheral blood T- and B-lymphocyte levels, as mentioned above, were found between the CN Collies and the normal Collie. The absolute B-lymphocyte counts for CN Collies also showed a statistically significant increase (P less than 0.005) over counts for the normal Collie, and daily changes in both B- and T-lymphocyte counts were always greater for CN Collies than for normal Collies.


Male genital schwannoma, review of 5 cases.
To study the clinical features of male genital schwannoma. Five male patients with genital schwannoma admitted from 1991 to 2000 were reviewed. The lesions were located in the prostate, spermatic cord, testis or penis. Tumors were simply resected in 3 patients and radically eradicated in 2. The average age of the cohort was 37 years. The most common sign at presentation was a palpable genital mass accidentally discovered by the patient or detected by the physician during a physical check. Diagnosis was made through postoperative pathological examination. Follow-up ranged from 2 years to 6 years (mean 4.5 years). Four cases were cured by simple excision and 1 patient with malignant testis schwannoma died of recurrence 1 year after surgery. Owing to the lack of characteristic clinical manifestation, the final diagnosis relies on postoperative pathological examination. S-100 and vimentin are useful markers for the diagnosis of these tumors.


Histone phosphorylation in macro- and micronuclei of Tetrahymena thermophila.
The patterns of histone phosphorylation in amitotically dividing, transcriptionally active macronuclei and in mitotically dividing, transcriptionally inert micronuclei of the ciliated protozoan Tetrahymena thermophila have been analyzed. Taken together, the major phosphorylation events in these two nuclei and their dependence on cell growth and/or division are remarkably similar to those in mammalian cells. Phosphorylation of H1-type proteins occurs in both nuclei and is positively correlated with growth and/or division. Phosphorylation of histone H3 is also positively correlated with growth and/or division but occurs only in micronuclei. Phosphorylation of histone H2A is relatively independent of growth state and occurs largely, if not exclusively, in macronuclei. Given the unique partition of nuclear functions between macro- and micronuclei, these results, coupled with previously reported temporal correlations between specific histone phosphorylations and cell cycle events in mammalian cells [Gurley, L. R., Tobey, R. A., Walters, R. A., Hildebrand, C. E., Hohmann, P. G., D'Anna, J. A., Barham, S. S., & Deaven, L. L. (1978a) in Cell Cycle Regulation (Jeter, J. R., Cameron, J. L., Padilla, G. M. & Zimmerman, A. M. Eds.) pp 37-60, Academic Press, New York], allow insights into the functions of histone phosphorylations. Specifically, a nonmitotic function for extensive H1 phosphorylation and a unique mitotic function for H3 phosphorylation are clearly indicated. A new role for H2A phosphorylation in the regulation of transcriptional activity is also proposed.


Sweet Potato Leaf Feeding Decreases Cholesterol, Oxidative Stress and Thrombosis Formation in Syrian Hamsters with a High-Cholesterol Diet.
Nutritional strategies to reduce hyperlipidemia and the risk of cardiovascular disease are gaining more public favor and medical professionals' attention. The authors of this study explored the effect of sweet potato leaf powder (SPLP) feeding on the parameters of plasma lipids, reactive oxygen species, and time to thrombosis formation in Syrian hamsters fed with high-cholesterol diets. The animals were separated into six groups: a feeding control diet, a control diet containing 0.1% cholesterol, a control diet containing 0.2% cholesterol, a control diet containing 0.1% cholesterol plus 2.5% SPLP, a control diet containing 0.1% cholesterol plus 5% SPLP, and a control diet containing 0.2% cholesterol plus 5% SPLP for six weeks. The levels of serum total cholesterol (51% increase), low-density lipoprotein cholesterol (70.6% increase), very-low-density lipoprotein cholesterol (51.3% increase), and the triglyceride and atherogenic index (LDL-C/HDL-C) significantly increased in the high-cholesterol diet groups. Concomitant 5% sweet potato leaf powder ingestion significantly decreased the lipid profiles, with a 20.6% total cholesterol reduction in the 0.1% cholesterol diet groups, a 17.2% reduction in the 0.2% group, a 48.7% LDL reduction in the 0.1% cholesterol group, and a 30.3% reduction in the 0.2% group, with a consequent decrease in the atherogenic index. SPLP feeding was found to be associated with increased fecal sterol contents, with a 188.6% increase in the 0.1% cholesterol-fed group and a 177.3% increase in the 0.2% group. The SPLP-fed groups had depressed ROS levels, elongated FeCl3-induced times to thrombosis formation, and increased liver superoxide dismutase contents and SREBP-1 protein expression. Sweet potato leaf intake could reduce plasma total cholesterol, LDL, and oxidative stress. We suggest sweet potato leaf intake as a choice of nutritional strategy for hyperlipidemia and cardiovascular disease prevention.


People's experiences of hospital care on the weekend: secondary analysis of data from two national patient surveys.
To determine whether patients treated in hospital on the weekend report different experiences of care compared with those treated on weekdays. This is a secondary analysis of the 2014 National Health Service (NHS) adult inpatient survey and accident and emergency (A&E) department surveys. Differences were tested using independent samples t-tests and multiple regression, adjusting for patient age group, sex, ethnicity, proxy response, NHS trust, route of admission (for the inpatient survey) and destination on discharge (for the A&E survey). The inpatient survey included 154 NHS hospital trusts providing overnight care; the A&E survey 142 trusts with major emergency departments. Three cohorts were analysed: patients attending A&E, admitted to hospital and discharged from hospital. From the inpatient survey's 59 083 responses, 10 382 were admitted and 11 542 discharged on weekends or public holidays. The A&E survey received 39 320 responses, including 11 542 (29.4%) who attended on the weekend or on public holidays. Weekday and weekend attendees' response rates were similar once demographic characteristics were accounted for. For the A&E survey, six composite dimensions covered waiting times, doctors and nurse, care and treatment, cleanliness, information on discharge, and overall experiences. For the inpatient survey, three questions covered admissions and two dimensions covered information about discharge and about medicines. People attending A&E on weekends were significantly more favourable about 'doctors and nurses' and 'care and treatment'. Inpatients admitted via A&E on a weekend were more positive about the information given to them in A&E than others. Other dimensions showed no differences between people treated on weekdays or on weekends. Patients attending emergency departments or admitted to or discharged from an inpatient episode on weekends and public holidays report similar or more positive experiences of care to other patients after adjusting for patient characteristics.


Prehospital noninvasive ventilation for acute respiratory failure: systematic review, network meta-analysis, and individual patient data meta-analysis.
This meta-analysis aimed to determine the effectiveness of prehospital continuous positive airway pressure (CPAP) or bilevel inspiratory positive airway pressure (BiPAP) in acute respiratory failure. Fourteen electronic databases and research registers were searched from inception to August 2013. Randomized or quasi-randomized controlled trials that reported mortality or intubation rate for prehospital CPAP or BiPAP were selected and compared to a relevant comparator in patients with acute respiratory failure. An aggregate data network meta-analysis was used to jointly estimate intervention effects relative to standard care. A network meta-analysis using a mixture of individual patient-level data and aggregate data was carried out to assess potential treatment effect modifiers. Eight randomized and two quasi-randomized controlled trials (six CPAP, four BiPAP, sample sizes 23 to 207) were identified. The aggregate data network meta-analysis suggested that CPAP was the most effective treatment in terms of mortality (probability = 0.989) and intubation rate (probability = 0.639) and reduced both mortality (odds ratio [OR] = 0.41; 95% credible interval [CrI] = 0.20 to 0.77) and intubation rate (OR = 0.32; 95% CrI = 0.17 to 0.62), compared to standard care. The effect of BiPAP on mortality (OR = 1.94; 95% CrI = 0.65 to 6.14) and intubation rate (OR = 0.40; 95% CrI = 0.14 to 1.16) was uncertain. The network meta-analysis using individual patient-level data and aggregate data suggested that sex was a modifier of the effect of treatment on mortality. Prehospital CPAP can reduce mortality and intubation rates compared to standard care, while the effectiveness of prehospital BiPAP is uncertain.


Unusual behavior of MgFe2O4 during regeneration: desorption versus specific adsorption.
The reusability of spent adsorbents is the most important characteristic for their practical application. The process of MgFe2O4 regeneration after methylene blue (MB) adsorption was studied. The effect of the nature (HCl, HNO3, and MgCl2) and the concentration (10-3-10-1 M) of regeneration agents was established. All the regeneration agents at 10-3 and 10-2 M had high efficiency and adsorption capacity recovery reached 80-90%, whereas for 10-1 M concentration the adsorption efficiency was in the range of 4.5-36.2%. It was shown that the concentration of desorbed MB was much less than what had been previously adsorbed and did not correlate with regeneration efficiency. The unusual behavior of MgFe2O4 during regeneration could be due to different mechanisms of regeneration by OH3 + and Mg2+ ions: (i) for acidic regeneration the main process was the non-specific adsorption of OH3 + ions in a diffusion layer and the substitution of adsorbed MB due to electrostatic forces; (ii) in the case of Mg2+ as a regeneration agent, there was specific adsorption due to the completion of a crystal lattice of MgFe2O4 nanoparticles by Mg2+ ions (according to the rules of Fayans-Pannet) with the formation of new Mg-OH adsorption sites and the super-equivalent adsorption of Mg2+ ions (according to DLVO (Derjaguin, Landau, Verwey, and Overbeek) theory) accompanied by a recharge of the MgFe2O4 surface. These phenomena of MgFe2O4 regeneration using Mg2+ ions must be taken into account in the theory and practice of adsorption.


[The correlation of the psychological and hormonal status in obese patients].
A study was made of psychological personality traits and their relationship with hormonal-lipid interrelations in patients with different types of obesity. The MMPI methods, modified by F. B. Berezin, were employed. A group of 80 patients was investigated. A significant rise of the level of the 7th and 8th MMPI scales was revealed in patients with hypothalamic obesity (HO) as compared to patients with alimentary constitutional obesity (ACO). This rise could be accounted for by hypercorticism in HO patients and the adaptogenic effect of cortisol. It was also confirmed by the presence of a feedback between cortisol levels and MMPI scales 1, 2, 6. Negative interrelationships between value 0 of the MMPI test scale and the level of basal oxygen metabolism were indicative of the significance of redox processes in social adaptation. ACO women were shown to have a high level of adaptation to stress agents as compared to ACO men. In menopausal ACO women a rise of scales 7 and 8 was observed, a rise of scales 2 and 7--in HO, indicating adaptation failure and proving the adaptation role of estrogens in responses of the body to stress.


Kinematic control of redundant robots and the motion optimizability measure.
This paper treats the kinematic control of manipulators with redundant degrees of freedom. We derive an analytical solution for the inverse kinematics that provides a means for accommodating joint velocity constraints in real time. We define the motion optimizability measure and use it to develop an efficient method for the optimization of joint trajectories subject to multiple criteria. An implementation of the method for a 7-dof experimental redundant robot is present.


Sleepiness, quality of life, and sleep maintenance in REM versus non-REM sleep-disordered breathing.
The impact of REM-predominant sleep-disordered breathing (SDB) on sleepiness, quality of life (QOL), and sleep maintenance is uncertain. To evaluate the association of SDB during REM sleep with daytime sleepiness, health-related QOL, and difficulty maintaining sleep, in comparison to their association with SDB during non-REM sleep in a community-based cohort. Cross-sectional analysis of 5,649 Sleep Heart Health Study participants (mean age 62.5 [SD = 10.9], 52.6% women, 22.6% ethnic minorities). SDB during REM and non-REM sleep was quantified using polysomnographically derived apnea-hypopnea index in REM (AHI(REM)) and non-REM (AHI(NREM)) sleep. Sleepiness, sleep maintenance, and QOL were respectively quantified using the Epworth Sleepiness Scale (ESS), the Sleep Heart Health Study Sleep Habit Questionnaire, and the physical and mental composites scales of the Medical Outcomes Study Short Form (SF)-36. AHI(REM) was not associated with the ESS scores or the physical and mental components scales scores of the SF-36 after adjusting for demographics, body mass index, and AHI(NREM) x AHI(REM) was not associated with frequent difficulty maintaining sleep or early awakening from sleep. AHI(NREM) was associated with the ESS score (beta = 0.25; 95% confidence interval [CI], 0.16 to 0.34) and the physical (beta = -0.12; 95% CI, -0.42 to -0.01) and mental (beta = -0.20; 95% CI, -0.20 to -0.01) components scores of the SF-36 adjusting for demographics, body mass index, and AHI(REM). In a community-based sample of middle-aged and older adults, REM-predominant SDB is not independently associated with daytime sleepiness, impaired health-related QOL, or self-reported sleep disruption.


Data of self-made Taq DNA polymerase prepared for screening purposes.
DNA analysis is a key procedure in genetic engineering. Nowadays the analysis is often done by PCR with Taq DNA polymerase. Although the last enzyme price is quite low, demand for numerous analyses results in much money expenditure which are not affordable for many laboratories. In a meanwhile, many screening tasks do not require the highly purified enzyme. Taking into account the enzyme unique properties it makes possible to marginally simplify its production without resorting to costly or lengthy techniques such as column chromatography and/or dialysis. Here the data of routine usage of Taq DNA polymerase prepared according to the protocol developed in our laboratory is presented. The protocol takes only several hours to realize and does not need qualified personnel or expensive equipment. Yet it gives the enzyme preparation suitable for most screening purposes. The isolated Taq DNA polymerase stock can be stored as ammonium sulfate suspension in a refrigerator for prolonged period, not less than 6 months. The working enzyme solution is prepared from the stock suspension on demand, not more than once in a month and can be stored also in a refrigerator.


Identifying training needs for mainstream healthcare professionals, to prepare them for working with individuals with intellectual disabilities: a systematic review.
Research suggests there is a high prevalence of physical and mental ill health among individuals with intellectual disabilities and that staff working in mainstream healthcare services lack knowledge, skills and positive attitudes in supporting this client group. This review aimed to locate, extract themes from and evaluate the current literature that had assessed the training needs of mainstream health professionals within this area. This review utilized a mixed-methods approach, with systematic elements used to locate and evaluate the literature (n = 13) and a narrative approach used to explore patterns and themes identified. The search was completed across four databases, using the search terms felt most likely to capture the relevant literature. Three main themes of perceived training need were identified across a range of professional groups: general communication, knowledge/information and profession-specific needs. This review highlights the existing themes of training needs as identified by mainstream healthcare staff. It would appear that it may be possible to produce a core training package, suitable across professions with elements that are profession specific and therefore tailored accordingly. Limitations of the literature are explored within this review, as are recommendations for the directions of future research.


Identification of tribbles homolog 2 as an autoantigen in autoimmune uveitis by phage display.
Autoimmune uveitis is a group of ocular inflammatory disorders with unknown causes. As in other autoimmune diseases, identification of autoantigens from uveitis patients would markedly improve our understanding of the disease mechanism. Here, we report that a candidate autoantigen was identified by phage display in an unbiased fashion. A bacteriophage T7 display cDNA library was generated from human eye and characterized. Patient-specific phages were enriched by four rounds of phage display with purified patient IgG. Enriched phages demonstrated a 20-fold increase in binding specificity to the patient IgG compared with control IgG. Two clonal phages with particularly high relative binding specificities were isolated and characterized. The encoded genes, tribbles homolog 2 (TRB2) and an unknown protein, had 170- and 42-fold increases in their binding specificities to the patient IgG, respectively. The patient-specific immunoreactivities were further confirmed by Western blotting. Anti-TRB2 antibody activities were detected in several uveitis patients but not in control subjects, suggesting that TRB2 is a uveitis-associated candidate autoantigen. These results demonstrate that autoantigens can be identified by phage display using uveitis patient serum.


[Cellular Composition of Calcified Bioprosthetic Heart Valves].
With the aim to assess the mechanisms of the structural dysfunctions associated with xenograft tissue calcification, we investigated the cellular composition of the explanted xenoaortic epoxy-treated bioprosthetic heart valves. In the leaflets, we revealed multiple cells with retained internal structure. Most of them located on the leaflet surface, at the areas of collagen destruction, and near calcium deposits. Monocytes were the predominant cell fraction on the leaflet surface whilst immune (macrophages, multinucleated giant cells, plasma cells, neutrophils) and connective tissue (fibroblasts, fibrocytes, endothelial, and smooth muscle cells) cells prevailed at the areas of collagen destruction and near calcium deposits. Calcification of the leaflets was accompanied by cellular infiltration, therefore suggesting that pathological mineralization may be associated with cell-mediated processes.


The effect of nadolol on heart rate in hyperthyroidism. A controlled trial.
Twenty hyperthyroid patients were randomly assigned in a double-blind fashion to receive either nadolol 80 mg/day or placebo for 2 weeks; all patients then took carbimazole as well from 2-6 weeks. Twenty-four hour Holter ECG recordings at 0, 2 and 6 weeks showed that nadolol reduced the mean maximum heart rate by 19.9% (P less than 0.0005) at 2 weeks and by 30.3% (P less than 0.0005) at 6 weeks compared to 5.2% (ns) and 18.3% (P less than 0.0005) in patients taking placebo. There was no alteration of the normal circadian variation of heart rate by nadolol. The minimum heart rate before therapy was significantly correlated with FT4 (r = 0.52) and with FT3 (r = 0.44). The percentage of time per hour during which the heart rate was greater than 100 was reduced by 79% at week 2 by nadolol compared to 22% in the placebo group. At the 6 week point the placebo group still had a tachycardia (mean maximum heart rate 101.6 beats/min +/- 15.2 SD) compared to the nadolol group (80.4 +/- 7.7). Nadolol did not cause excessive bradycardia. It is effective in the early management of hyperthyroidism and should be given for at least the first 4-6 weeks.


Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck.
Oncogenic human papillomaviruses (HPVs), especially HPV type 16 (HPV-16), cause anogenital epithelial cancers and are suspected of causing epithelial cancers of the head and neck. To examine the relation between head and neck cancers and HPVs, we performed a nested case-control study within a joint Nordic cohort in which serum samples were collected from almost 900,000 subjects. Samples collected at enrollment from 292 persons in whom squamous-cell carcinoma of the head and neck developed, on average, 9.4 years after enrollment and from 1568 matched controls were analyzed for antibodies against HPV-16, HPV-18, HPV-33, and HPV-73 and for cotinine levels as a marker of smoking habits. Polymerase-chain-reaction (PCR) analyses for HPV DNA were performed in tumor tissue from 160 of the study patients with cancer. After adjustment for cotinine levels, the odds ratio for squamous-cell carcinoma of the head and neck in subjects who were seropositive for HPV-16 was 2.2 (95 percent confidence interval, 1.4 to 3.4). No increased risk was observed for other HPV types. Fifty percent of oropharyngeal and 14 percent of tongue cancers contained HPV-16 DNA, according to PCR analysis. HPV-16 infection may be a risk factor for squamous-cell carcinoma of the head and neck.


The β-carboline alkaloid harmine inhibits telomerase activity of MCF-7 cells by down-regulating hTERT mRNA expression accompanied by an accelerated senescent phenotype.
The end replication problem, which occurs in normal somatic cells inducing replicative senescence, is solved in most cancer cells by activating telomerase. The activity of telomerase is highly associated with carcinogenesis which makes the enzyme an attractive biomarker in cancer diagnosis and treatment. The indole alkaloid harmine has multiple pharmacological properties including DNA intercalation which can lead to frame shift mutations. In this study, harmine was applied to human breast cancer MCF-7 cells. Its activity towards telomerase was analyzed by utilizing the telomeric repeat amplification protocol (TRAP). Our data indicate that harmine exhibits a pronounced cytotoxicity and induces an anti-proliferation state in MCF-7 cells which is accompanied by a significant inhibition of telomerase activity and an induction of an accelerated senescence phenotype by over-expressing elements of the p53/p21 pathway.


A New Chemical Pathway Yielding A-Type Vitisins in Red Wines.
A new chemical pathway yielding A-type vitisins in red wines is proposed herein from the reaction between anthocyanins and oxaloacetic acid (OAA). This new chemical path is thought to occur in the first stages of the wine production even during the fermentation process. This is due to the revealed high reactivity of OAA with anthocyanins compared with the already known precursor (pyruvic acid, PA). In model solutions at wine pH (3.5), when malvidin-3-O-glucoside (mv-3-glc) is in contact with OAA and PA a decrease in the OAA concentration is observed along with the formation of A-type vitisin. Moreover, part of the OAA is also chemically converted into PA in model solutions. The reaction yields were also determined for OAA and PA using different mv-3-glc:organic acid molar ratios (1:0.5, 1:1, 1:5, 1:10; 1:50, and 1:100) and these values were always higher for OAA when compared to PA, even at the lowest molar ratio (1:0.5). The reaction yields were higher at pH 2.6 in comparison to pH 1.5 and 3.5, being less affected at pH 3.5 for OAA. These results support the idea that OAA can be at the origin of A-type vitisins in the first stages of wine production and PA in the subsequent ageing process.


Influence of frontal-to-parietal connectivity in pseudoneglect: A cortico-cortical paired associative stimulation study.
Pseudoneglect is a set of visuospatial biases that entails a behavioral advantage for stimuli appearing in the left hemifield compared to the right one. Although right hemisphere dominance for visuospatial processing has been invoked to explain this phenomenon, its neurophysiological mechanisms are still debated, and the role of intra- and inter-hemispheric connectivity is yet to be defined. The present study explored the possibility of modulating pseudoneglect in healthy participants through a cortico-cortical paired associative stimulation protocol (ccPAS): a non-invasive brain stimulation protocol that manipulates the interplay between brain regions through the repeated, time-locked coupling of two transcranial magnetic stimulation (TMS) pulses. In the first experiment, healthy participants underwent a frontal-to-parietal (FP) and a parietal-to-frontal (PF) ccPAS. In the FP protocol, the first TMS pulse targeted the right frontal eye field (FEF), and the second pulse the right inferior parietal lobule (IPL), two critical areas for visuospatial and attentional processing. In the PF condition, the order of the pulses was reversed. In both protocols, the inter-stimulus interval (ISI) was 10 ms. Before and after stimulation, pseudoneglect was assessed with a landmark task and a manual line bisection task. A second experiment controlled for ccPAS timing dependency by testing FP-ccPAS with a longer ISI of 100 ms. Results showed that after administering the FP-ccPAS with the ISI of 10 ms, participants' leftward bias in the landmark task increased significantly, with no effects in the manual line bisection task. The other two protocols tested were ineffective. Our findings showed that ccPAS could be used to modulate pseudoneglect by exploiting frontal-to-parietal connectivity, possibly through increased top-down attentional control. FP-ccPAS could represent a promising tool to investigate connectivity properties within visuospatial and attentional networks in the healthy and as a potential rehabilitation protocol in patients suffering from severe visuospatial pathologies.


[Exercise as the cornerstone of cardiovascular prevention].
Lack of physical activity in the general population is a public health problem and is recognized as an independent risk factor for the development of coronary disease. The relative risk of inactivity is similar to that of hypertension, hypercholesterolemia and smoking. Consequently, a sedentary lifestyle is associated with a concurrent increase in cardiovascular disease. Engaging regularly in mild-to-moderate physical exercise results in a range of physiological adaptations that are beneficial for health. Various studies have demonstrated that there is an inverse relationship between regular exercise and the risk of coronary heart disease, cardiac events and death. Exercise improves the lipid profile and glycemic control, reduces or prevents hypertension, obesity and stress, and promotes fitness and longevity. However, most evidence for the benefits of exercise comes from observational studies and, although maximum oxygen uptake and the duration of exercise on an exercise stress test are powerful predictors of mortality, there is no agreement on the quantity or intensity of the physical activity needed for primary or secondary prevention. On the other hand, although there is a temporarily increased risk of acute myocardial infarction during exhaustive exercise, the balance of risks and benefits is strongly in favor of the benefits because there is a minimum threshold for the weekly energy expenditure required to reduce cardiovascular risk.


Effect of guanine to inosine substitution on stability of canonical DNA and RNA duplexes: molecular dynamics thermodynamics integration study.
Guanine to inosine (G → I) substitution has often been used to study various properties of nucleic acids. Inosine differs from guanine only by loss of the N2 amino group, while both bases have similar electrostatic potentials. Therefore, G → I substitution appears to be optimally suited to probe structural and thermodynamics effects of single H-bonds and atomic groups. However, recent experiments have revealed substantial difference in free energy impact of G → I substitution in the context of B-DNA and A-RNA canonical helices, suggesting that the free energy changes reflect context-dependent balance of energy contributions rather than intrinsic strength of a single H-bond. In the present study, we complement the experiments by free energy computations using thermodynamics integration method based on extended explicit solvent molecular dynamics simulations. The computations successfully reproduce the basic qualitative difference in free energy impact of G → I substitution in B-DNA and A-RNA helices although the magnitude of the effect is somewhat underestimated. The computations, however, do not reproduce the salt dependence of the free energy changes. We tentatively suggest that the different effect of G → I substitution in A-RNA and B-DNA may be related to different topologies of these helices, which affect the electrostatic interactions between the base pairs and the negatively charged backbone. Limitations of the computations are briefly discussed.


Diffusion Tensor Magnetic Resonance Imaging Strategies for Color Mapping of Human Brain Anatomy.
A color mapping of fiber tract orientation using diffusion tensor imaging (DTI) can be prominent in clinical practice. The goal of this paper is to perform a comparative study of visualized diffusion anisotropy in the human brain anatomical entities using three different color-mapping techniques based on diffusion-weighted imaging (DWI) and DTI. The first technique is based on calculating a color map from DWIs measured in three perpendicular directions. The second technique is based on eigenvalues derived from the diffusion tensor. The last technique is based on three eigenvectors corresponding to sorted eigenvalues derived from the diffusion tensor. All magnetic resonance imaging measurements were achieved using a 1.5 Tesla Siemens Vision whole body imaging system. A single-shot DW echoplanar imaging sequence used a Stejskal-Tanner approach. Trapezoidal diffusion gradients are used. The slice orientation was transverse. The basic measurement yielded a set of 13 images. Each series consists of a single image without diffusion weighting, besides two DWIs for each of the next six noncollinear magnetic field gradient directions. The three types of color maps were calculated consequently using the DWI obtained and the DTI. Indeed, we established an excellent similarity between the image data in the color maps and the fiber directions of known anatomical structures (e.g., corpus callosum and gray matter). In the meantime, rotationally invariant quantities such as the eigenvectors of the diffusion tensor reflected better, the real orientation found in the studied tissue.


[Pulmonary arterial hypertension due to the use of amphetamines as drugs or doping].
Pulmonary arterial hypertension (PAH) was diagnosed in three patients. All three had a history ofamphetamine consumption. The patients were a 48-year-old male drug addictwho had used intravenous amphetamine for more than 20 years, a 43-year-old man who had been administered intravenous amphetamines during a period of intensive cycling and a 34-year-old woman who regularly consumed amphetamine at dance festivals. All three patients received medicinal treatment. Amphetamines may lead to PAH due to the release of serotonin, which causes pulmonary vasoconstriction and the proliferation of smooth muscle cells. Due to the pathophysiology of amphetamine-induced PAH, other amphetamine derivatives such as methylenedioxymethamphetamine (ecstasy) and methylphenidate can be risk factors for PAH. These three cases show that PAH should be considered in patients who present with dyspnoea and a reduced exertion tolerance, and who are known to have a history of amphetamine use.


Predictors of Hand-Foot Syndrome and Pyridoxine for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Randomized Clinical Trial.
Hand-foot syndrome (HFS) is a common adverse effect of capecitabine treatment. To compare the incidence and time to onset of grade 2 or greater HFS in patients receiving pyridoxine vs placebo and to identify biomarkers predictive of HFS. This single-center, randomized double-blind, placebo-controlled phase 3 trial conducted at National Cancer Centre Singapore assessed whether oral pyridoxine could prevent the onset of grade 2 or higher HFS in 210 patients scheduled to receive single-agent capecitabine chemotherapy for breast, colorectal, and other cancers. Patients were randomized to receive concurrent pyridoxine (200 mg) or placebo daily for a maximum of 8 cycles of capecitabine, with stratification by sex and use in adjuvant or neoadjuvant vs palliative setting. Patients were withdrawn from the study on development of grade 2 or higher HFS or cessation of capecitabine. Primary end point was the incidence of grade 2 or higher HFS in patients receiving pyridoxine. Secondary end points included the time to onset (days) of grade 2 or higher HFS and identification of biomarkers predictive of HFS, including baseline folate and vitamin B12 levels, as well as genetic polymorphisms with genome-wide arrays. In this cohort of 210 patients (median [range] age, 58 [26-82] years; 162 women) grade 2 or higher HFS occurred in 33 patients (31.4%) in the pyridoxine arm vs 39 patients (37.1%) in the placebo arm (P = .38). The median time to onset of grade 2 or higher HFS was not reached in both arms. In univariate analysis, the starting dose of capecitabine (odds ratio [OR], 1.99; 95% CI, 1.32-3.00; P = .001), serum folate levels (OR, 1.27; 95% CI, 1.10-1.47; P = .001), and red blood cell folate levels (OR, 1.25; 95% CI, 1.08-1.44; P = .003) were associated with increased risk of grade 2 or higher HFS. In multivariate analyses, serum folate (OR, 1.30; 95% CI, 1.12-1.52; P < .001) and red blood cell folate (OR, 1.28; 95% CI, 1.10-1.49; P = .001) were the only significant predictors of grade 2 or higher HFS. Grade 2 or higher HFS was associated with 300 DNA variants at genome-wide significance (P < 5 × 10-8), including a novel DPYD variant (rs75267292; P = 1.57 × 10-10), and variants in the MACF1 (rs183324967, P = 4.80 × 10-11; rs148221738, P = 5.73 × 10-10) and SPRY2 (rs117876855, P < 1.01 × 10-8; rs139544515, P = 1.30 × 10-8) genes involved in wound healing. Pyridoxine did not significantly prevent or delay the onset of grade 2 or higher HFS. Serum and red blood cell folate levels are independent predictors of HFS. clinicaltrials.gov Identifier: NCT00486213.


Effect of zinc on liver cirrhosis with hyperammonemia: a preliminary randomized, placebo-controlled double-blind trial.
To our knowledge, no randomized study has shown whether zinc replacement therapy is effective for hyperammonemia in liver cirrhosis; therefore, we performed a double-blind, placebo-controlled trial to examine efficacy and safety of the zinc replacement therapy. Patients with liver cirrhosis and hyperammonemia (at or above the institutional reference value) and hypozincemia (≤65 μg/dL) were enrolled in the outpatient units of the participating institutions and were randomly divided to receive placebo (P group) or zinc acetate preparation at a dose of 3 capsules/d for a total zinc content of 150 mg/d (Z group) by the envelope method. Of the 18 enrolled patients, 6 dropped out; thus, the analyses included 12 patients (5 in the P group and 7 in the Z group). Variations in blood concentrations of zinc and ammonia as well as liver function test results were compared. Blood zinc levels significantly increased in the Z group (P = 0.0037; Friedman test) but not the P group. Blood ammonia levels significantly decreased in the Z group (P = 0.0114; Friedman test) but not the P group. The percent change in blood ammonia level also revealed significant reduction at the eighth week in the Z group (P = 0.0188: Mann-Whitney test). No serious adverse events attributable to the zinc preparation were noted. Although this study is preliminary and includes a small sample, it is, to our knowledge, the first randomized controlled trial to show that zinc supplementation for 3 mo seems effective and safe for treating hyperammonemia in liver cirrhosis. Studies with a larger sample size are needed to confirm our findings.


Current status of functional gastrointestinal evaluation in clinical practice.
Neurogastroenterology and motility disorders of the gastrointestinal (GI) tract encompass a broad spectrum of diseases involving the GI tract and central nervous system. They have varied pathophysiology, clinical presentation and management, and make up a substantial proportion of outpatient clinic visits. Typically, patients experience persistent symptoms referable to the GI tract despite normal endoscopic and radiologic findings. An appropriate evaluation is thus important in the patient's care. Advances in technology and understanding of the disease pathophysiology have provided better insight into the physiological basis of disease and a more rational approach to patient management. While technological advances serve to explain patients' persistent symptoms, they should be balanced against the costs of diagnostic tests. This review highlights the GI investigative modalities employed to evaluate patients with persistent GI symptoms in the absence of a structural lesion, with particular emphasis on investigative modalities available locally and the clinical impact of such tools.


Examination of geometric and dosimetric accuracies of gated step-and-shoot intensity modulated radiation therapy.
Due to the complicated technical nature of gated radiation therapy, electronic and mechanical limitations may affect the precision of delivery. The purpose of this study is to investigate the geometric and dosimetric accuracies of gated step-and-shoot intensity modulated radiation treatments (SS-IMRT). Unique segmental MLC plans are designed, which allow quantitative testing of the gating process. Both ungated and gated deliveries are investigated for different dose sizes, dose rates, and gating window times using a commercial treatment system (Varian Trilogy) together with a respiratory gating system [Varian Real-Time Position Management system]. Radiographic film measurements are used to study the geometric accuracy, where it is found that with both ungated and gated SS-IMRT deliveries the MLC leaf divergence away from planned is less than or equal to the MLC specified leaf tolerance value for all leafs (leaf tolerance being settable from 0.5-5 mm). Nevertheless, due to the MLC controller design, failure to define a specific leaf tolerance value suitable to the SS-IMRT plan can lead to undesired geometric effects, such as leaf motion of up to the maximum 5 mm leaf tolerance value occurring after the beam is turned on. In this case, gating may be advantageous over the ungated case, as it allows more time for the MLC to reach the intended leaf configuration. The dosimetric precision of gated SS-IMRT is investigated using ionization chamber methods. Compared with the ungated case, it is found that gating generally leads to increased dosimetric errors due to the interruption of the "overshoot phenomena." With gating the average timing deviation for intermediate segments is found to be 27 ms, compared to 18 ms for the ungated case. For a plan delivered at 600 MU/min this would correspond to an average segment dose error of approximately 0.27 MU and approximately 0.18 MU for gated and ungated deliveries, respectively. The maximum dosimetric errors for individual intermediate segments are found to deviate by up to approximately 0.64 MU from their planned value when delivered at 600 MU/min using gating, this compares to only approximately 0.32 MU for the ungated case.


The influence of news events on health after disaster: a longitudinal study in general practice.
This study investigates the influence of local and international news events on utilization of health services resources and health complaints as presented by victims of a fireworks depot disaster. It was hypothesized that victims (N = 2,854) will show more utilization and health complaints to their general practitioner (GP) in the week after 11 local news reports of events relating to the specific index trauma and 6 unrelated disasters reported in international print news, than the week before. Health data of victims and matched controls were extracted from electronic medical records, covering 4-years postdisaster. Especially local news events concerning the cause of the disaster were associated in both victims and controls with an increase of GP utilization and health complaints, including medically unexplained physical symptoms, chronic diseases, and psychological problems. No difference between victims and controls were found.


Familial Risk and Interaction With Smoking and Alcohol Consumption in Bladder Cancer: A Population-Based Cohort Study.
Although genetic factors are known to play a role in the pathogenesis of bladder cancer, population-level familial risk estimates are scarce. We aimed to quantify the familial risk of bladder cancer and analyze interactions between family history and smoking or alcohol consumption. Using the National Health Insurance database, we constructed a cohort of 5,524,403 study subjects with first-degree relatives (FDRs) and their lifestyle risk factors from 2002 to 2019. Familial risk was calculated using hazard ratios (HRs) with 95% confidence intervals (CIs) that compare the risk of individuals with and without affected FDRs. Interactions between family history and smoking or alcohol intake were assessed on an additive scale using the relative excess risk due to interaction (RERI). Offspring with an affected parent had a 2.09-fold (95% CI: 1.41 - 3.08) increased risk of disease compared to those with unaffected parents. Familial risks of those with affected father and mother were 2.26 (95% CI: 1.51 - 3.39) and 1.10 (95% CI: 0.27 - 4.41), respectively. When adjusted for lifestyle factors, HR reduced slightly to 2.04 (95% CI: 1.38 - 3.01), suggesting that a genetic predisposition is the main driver in the familial aggregation. Smokers with a positive family history had a markedly increased risk of disease (HR: 3.60, 95% CI: 2.27 - 5.71), which exceeded the sum of their individual risks, with statistically significant interaction (RERI: 0.72, 95% CI: 0.31 - 1.13). For alcohol consumption, drinkers with a positive family history also had an increased risk of disease, although the interaction was not statistically significant (RERI: 0.05, 95% CI: -3.39 - 3.48). Smokers and alcohol consumers with a positive family history of bladder cancer should be considered a high-risk group and be advised to undergo genetic counseling.


Distinct chromosomal imbalances in uterine serous and endometrioid carcinomas.
Endometrial carcinoma shows various histological types that differ in their clinical presentation and prognosis. Comparative genomic hybridization was used to detect gains and losses of DNA sequences along all chromosome arms in 24 uterine serous and 24 uterine endometrioid carcinomas. In serous carcinomas, extensive genetic aberrations were detected in 17 of the 24 specimens, with a mean of 5.7 changes per tumor. The most frequent gains occurred at 3q (50%), 8q (33%), 5p (29%), 6p (29%), and 1q (29%), and the most common losses were located at 4q (17%), 15q (17%), and 18q (17%). Tumors exhibiting DNA copy number changes were associated with shorter overall survival. In endometrioid carcinomas, genetic aberrations were less frequent and simpler than in serous carcinomas. DNA sequence copy number changes were observed in 12 of the 24 cases, with a mean of 1.5 changes per tumor. The most frequent aberrations were gains at 1q (29%), 2q (13%), and 8q (13%). Losses were rarely observed. The diverging pattern of genetic changes observed in uterine serous and endometrioid carcinomas suggests different pathways of carcinogenesis in these tumor types.


High-functioning autism and schizophrenia: a comparison of an early and late onset neurodevelopmental disorder.
Autism and schizophrenia are separate neurodevelopmental disorders that share a number of interpersonal and cognitive deficits. The symptoms of autism first appear during early life while schizophrenic symptoms do not typically appear until adolescence at the earliest. Efforts have been made to characterize the pattern of cognitive function in both disorders, and certain resemblances have become apparent such as deficits in abstract reasoning and the more complex aspects of memory and language. The present study provided a comparison of cognitive function between the two disorders. The autistic sample consisted of well-diagnosed individuals with high-functioning autism (IQ> or =70). The schizophrenic sample was divided into four subgroups using Ward's method of cluster analysis. Participants received the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Halstead Category Test, the Trail Making test, and the Wisconsin Card Sorting test (WCST). The profile of the autism sample was compared with the four schizophrenia cluster profiles. The autism group resembled only one of the schizophrenia clusters, with both showing elevations on the WAIS-R Information and Block Design subtests and depressions on Comprehension and Digit Symbol. It was concluded that individuals with high-functioning autism have a cognitive profile that resembles that of an empirically derived subgroup of schizophrenia patients but that does not resemble profiles found in other schizophrenia subgroups. The pattern itself, marked by a relatively depressed score on the Comprehension subtest among the Verbal subtests and a relatively elevated score on Block Design among the Performance subtests, has been characterized in the past as a prototypic profile for high-functioning autism.


[Temperature and humidity in the storage area of sterile materials: a literature review].
The recommendations for temperature (T°) and relative humidity (RU) for the storage of sterilized materials in Sterilization Central Supply (SCS) vary according to different sources, and are not based on theoretical frameworks or experiments. The practice shows difficulties in controlling these parameters, leading to doubts regarding the maintenance of the sterility of these materials. This article proposed, through a literature review, to identify and analyze the recommendations for T° and RU for the sterile storage area. We did not find any literature that justifies the referred recommendations. Seven articles were included which analyzed the variables T° and RU in the storage area as factors that could affect the sterility of the materials, and showed contradictory results regarding these factors' interference in maintaining the sterility of the materials.


Microarray data and pathway analyses of peripheral blood mononuclear cells from healthy subjects after a three weeks grape-rich diet.
Using Human Gene Expression Microarrays (Agilent) technologies, we investigated changes of the level of gene expression in peripheral blood mononuclear cells of healthy subjects after 21 days of fresh table grape-rich diet and after an additional 28-day washout. Several hundreds of genes were differentially expressed after grape intake or after washout. The functional analysis of these genes detected significant changes in key processes such as inflammation and immunity, thrombosis, DNA and protein repair, autophagy and mitochondrial biogenesis. Moreover, fresh grape intake was found to influence the expression of many long non-coding RNA genes. The data can be valuable for researchers interested in nutrigenetics and nutrigenomics studies and are related to the research article "Gene expression signature induced by grape intake in healthy subjects reveals wide-spread beneficial effects on PBMCs" [1].


Application of structured support vector machine backpropagation to a convolutional neural network for human pose estimation.
In this study, for the first time, we show how to formulate a structured support vector machine (SSVM) as two layers in a convolutional neural network, where the top layer is a loss augmented inference layer and the bottom layer is the normal convolutional layer. We show that a deformable part model can be learned with the proposed structured SVM neural network by backpropagating the error of the deformable part model to the convolutional neural network. The forward propagation calculates the loss augmented inference and the backpropagation calculates the gradient from the loss augmented inference layer to the convolutional layer. Thus, we obtain a new type of convolutional neural network called an Structured SVM convolutional neural network, which we applied to the human pose estimation problem. This new neural network can be used as the final layers in deep learning. Our method jointly learns the structural model parameters and the appearance model parameters. We implemented our method as a new layer in the existing Caffe library.


The abundance and in vitro DNA binding of three cellular proteins interacting with the adenovirus EIIa early promoter are not modified by the EIa gene products.
Specific protein binding on the EIa-inducible adenovirus EIIa early (EIIaE) promoter was analyzed by the sensitive electrophoretic band-shift assay and by protection against DNase I digestion. Three factors were identified, and precise mapping of the cognate-binding sites revealed their correspondence to promoter elements essential for constitutive EIIaE transcription. One binds to the major upstream element located between -82 and -64 (with respect to the major EIIaE cap site), another appears to interact with sequences on either side of this region, and the last one binds to an element located further upstream. Comparison of the binding activities of the factors present in extracts from cells infected with wild-type adenovirus (adenovirus type 5) or with the EIa deletion mutant dl312 did not reveal striking differences. Not only were the general binding patterns indistinguishable, but the concentration of each of the identified factors as well as their affinity for the cognate-binding sites were unchanged. Our results suggest that the EIa-mediated activation of the EIIaE transcription complexes involves appropriate interactions between transcription factors, rather than their increased binding to DNA.


Zinc oxide-ozonated olive oil as a new root canal filling material in primary molars: a clinical randomized controlled trial.
The complex root canal anatomy of primary teeth keeps it very tricky to attain appropriate cleansing by biomechanical instrumentation, so obtaining an obturating material with excellent antimicrobial properties is a challenge in current clinical pulpectomy practice. So, this study aimed to assess the clinical and radiographic performance of zinc oxide-ozonated olive oil as a primary root canal filling material. Ninety non-vital primary molars in children ranging from 4 to 8 years were allocated into three groups in which root canals were filled with zinc oxide-ozonated olive oil, zinc oxide-olive oil, and zinc oxide-eugenol (ZOE) according to each group after pulpectomy procedure. Clinical and radiographic evaluations were done at 3-, 6-, and 12-month follow-up periods. Statistical analysis was performed for the collected data. All study groups showed a significant improvement regarding clinical signs and symptoms during follow-up periods. Ozonated-olive oil group revealed a significant increase in furcation radiodensity and a decrease in periodontal ligament space at 3-, 6-, and 12-month follow-up intervals compared to other groups. Zinc oxide-ozonated olive oil and zinc oxide-olive oil paste had shown good clinical and radiographic success for primary teeth pulpectomy. The intricate torturous primary root canal anatomy, in addition to the child's negative behavior, interferes with the complete debridement, so the long-lasting antibacterial effect of the primary root canal filling material aids in the pulpectomy success.


The evidential value of dental calculus in the identification process.
DNA analysis-based identification is by far the gold standard in forensic genetics and it should be performed in every case involving human remains or unidentified bodies. Bones and teeth are the preferred source of human DNA for genetic analysis. However, there are cases where the nature of the proceedings and historical significance prevent the disruption of skeletal structure. The remains may also be heavily degraded. In such situations, forensic geneticists seek alternative sources of human DNA. Teeth calculus has proven to be a viable source of DNA for identification purposes. The aim of this study was to assess the concentration of human DNA in teeth calculus and evaluate the usefulness of teeth calculus as a DNA source in the identification process. Teeth calculus was collected from skeletons exhumed between 2021 and 2022 by the PBGOT (Polish Genetic Database of Victims of Totalitarianism) team from the former Stalag IID prisoner-of-war camp in Stargard. Genetic analyses included the determination of autosomal and Y-STR markers. The total concentration of human DNA was also evaluated in samples from teeth calculus and teeth taken from the same individuals. The pilot study included 22 skeletons with a sufficient amount of calculus for isolation (specified in the protocol). Samples were taken from the largest areas of calculus deposited on lingual surfaces of mandibular incisors. The prepared samples underwent DNA extraction. Our study demonstrated that teeth calculus is a source of human DNA for remains from the World War II period. The obtained DNA concentration allowed for the determination of STR markers. It was shown that teeth calculus contains human DNA in an amount suitable for preliminary identification analyses.


Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia.
In patients with severe eosinophilic asthma, local maturation rather than systemic recruitment of mature cells might contribute to persistent airway eosinophilia. Group 2 innate lymphoid cells (ILC2s) are a major source of type 2 cytokines (IL-5 and IL-13) and can facilitate eosinophilic inflammatory responses in mouse models of asthma in the absence of CD4+ lymphocytes. This study investigated the potential role of ILC2s in driving chronic airway eosinophilia in patients with severe asthma, despite regular high-dose oral corticosteroid therapy. In a cross-sectional study we enumerated blood and sputum ILC2s (lin(-)CD45(+)127(+)ST2(+)) and levels of intracellular IL-5 and IL-13 in patients with severe asthma (n = 25), patients with steroid-naive mild atopic asthma (n = 19), and nonatopic control subjects (n = 5). Results were compared with numbers of CD4+ lymphocytes, eosinophil lineage-committed progenitors (eosinophilopoietic progenitor cells [EoPs]), and mature eosinophils. Significantly greater numbers of total and type 2 cytokine-producing ILC2s were detected in blood and sputum of patients with severe asthma compared to mild asthmatics. In contrast, intracellular cytokine expression by CD4 cells and EoPs within the airways did not differ between the asthmatic groups. In patients with severe asthma, although sputum CD4+ cells were more abundant than ILC2s and EoPs, proportionally, ILC2s were the predominant source of type 2 cytokines. In addition, there were significantly greater numbers of sputum IL-5(+)IL-13(+) ILC2s in patients with severe asthma whose airway eosinophilia was greater than 3%, despite normal blood eosinophil numbers (<300/μL). Our findings suggest that ILC2s can promote the persistence of airway eosinophilia in patients with severe asthma through uncontrolled localized production of the type 2 cytokines IL-5 and IL-13, despite high-dose oral corticosteroid therapy.


The two major structural phosphoproteins (pp65 and pp150) of human cytomegalovirus and their antigenic properties.
Human cytomegalovirus (HCMV) purified from cell culture contains two dominant structural phosphoproteins with apparent molecular weights of 65,000 and 150,000, designated as pp65 and pp150 respectively. The humoral immune response of infected individuals against pp65 is relatively weak and is not always detectable by Western blot analyses. This report shows that recent clinical isolates of HCMV do not necessarily have pp65 as a prominent constituent, suggesting that the low immune reaction is due to variable expression of the pp65 in natural infections. However, the HCMV strains tested in this study produced the large structural phosphoprotein (pp150) in about equal amounts. The pp150 is remarkably immunogenic, if compared with all other virion constituents; serum pools and individual sera from HCMV-infected patients recognized this particular protein intensively in immunoblot assays. Thus, phosphoprotein pp150 seems to be the primary polypeptide candidate for expression cloning in order to develop reagents for novel ways of HCMV diagnosis.


[Breast carcinoma in men: a review of 21 cases].
Male breast carcinoma is a truly rare tumor the treatment and prognosis of which have been recently considered similar to female cancer. In this work we reviewed the clinical histories of 21 patients with breast cancer attended in our hospital over a period of fifteen years. Mean age was 60 years. The main cause of consult was the presence of painless nodules most frequently localized in the left breast. We have found a great latency period between the detection of the first symptoms and medical consult (almost 20 months) which by itself justifies that almost fifty percent of patients were either in stage III or IV. Global surveillance was 60% after 5 years excluding other causes of death that were not directly related with the tumor. Statistic analysis did not reveal any significant relationship, probably due to the small number of patients, between the prognosis of the disease and the presence of factors such as cutaneous involvement, duration of symptoms, thelorrhagia, patient age, lymph node [correction of ganglionar] involvement, or deep plane involvement, although a significant relationship (p less than 0.05) was found with TNM stage.


Micronutrient intakes from food and supplements in Australian adolescents.
Low micronutrient intakes in adolescents are frequently reported. We assessed micronutrient intakes in adolescents to determine whether supplement use optimises intakes. Dietary intake was assessed using a food frequency questionnaire in 17 year old participating in the Western Australian Pregnancy Cohort (Raine) Study (n=991). We calculated median daily micronutrient intakes in supplement users and non-users (from food sources only and from food and supplements), along with the percentage of adolescents meeting the Estimated Average Requirements (EAR) or Adequate Intake (AI) where appropriate. Intakes of calcium, magnesium, folate and vitamins D and E from food only were low. Although supplements significantly increased micronutrient intakes in supplement users, more than half of supplement users failed to meet the EAR or AI for some key micronutrients. Compared with non-users, supplement users had higher micronutrient intakes from food sources with the exception of vitamins D and B12 and were more likely to achieve the EAR or AI for many micronutrients from food only. Intakes of some key micronutrients were low in this population, even among supplement users. Those facing the greatest risk of micronutrient deficiencies were less likely to use supplements.


Raman spectroscopy and silver nanoparticles for efficient detection of membrane proteins in living cells.
Molecular fingerprints revealed by Raman techniques show great potential for biomedical applications, like disease diagnostic through Raman detection of tumor markers and other molecules in the cell membrane. However, SERS substrates used in membrane molecule studies produce enhanced Raman spectra of high variability and challenging band assignments that limit their application. In this work, these drawbacks are addressed to detect membrane-associated hemoglobin (Hbm) in human erythrocytes through Raman spectroscopy. These cells are incubated with silver nanoparticles (AgNPs) in PBS before Raman measurements. Our results showed that AgNPs form large aggregates in PBS that adhered to the erythrocyte membrane, which enhances Raman scattering by molecules around the membrane, like Hbm. Also, deoxyHb markers may allow Hbmdetection in Raman spectra of oxygenated erythrocytes (oxyRBCs). Raman spectra of oxyRBCs incubated with AgNPs showed enhanced deoxyHb signals with good spectral reproducibility, supporting the Hbmdetection through deoxyHb markers. Instead, Raman spectra of oxyRBCs showed oxyHb bands associated with free cytoplasmic hemoglobin. Other factors influencing Raman detection of membrane proteins are discussed, like bothz-position and dimension of the sample volume. The results encourage membrane protein studies in living cells using Raman spectroscopy, leading to the characterization and diagnostic of different pathologies through a non-invasive technique.


Functional characterisation of three members of the Vitis vinifera L. carotenoid cleavage dioxygenase gene family.
In plants, carotenoids serve as the precursors to C13-norisoprenoids, a group of apocarotenoid compounds with diverse biological functions. Enzymatic cleavage of carotenoids catalysed by members of the carotenoid cleavage dioxygenase (CCD) family has been shown to produce a number of industrially important volatile flavour and aroma apocarotenoids including β-ionone, geranylacetone, pseudoionone, α-ionone and 3-hydroxy-β-ionone in a range of plant species. Apocarotenoids contribute to the floral and fruity attributes of many wine cultivars and are thereby, at least partly, responsible for the "varietal character". Despite their importance in grapes and wine; carotenoid cleavage activity has only been described for VvCCD1 and the mechanism(s) and regulation of carotenoid catabolism remains largely unknown. Three grapevine-derived CCD-encoding genes have been isolated and shown to be functional with unique substrate cleavage capacities. Our results demonstrate that the VvCCD4a and VvCCD4b catalyse the cleavage of both linear and cyclic carotenoid substrates. The expression of VvCCD1, VvCCD4a and VvCCD4b was detected in leaf, flower and throughout berry development. VvCCD1 expression was constitutive, whereas VvCCD4a expression was predominant in leaves and VvCCD4b in berries. A transgenic population with a 12-fold range of VvCCD1 expression exhibited a lack of correlation between VvCCD1 expression and carotenoid substrates and/or apocarotenoid products in leaves, providing proof that the in planta function(s) of VvCCD1 in photosynthetically active tissue is distinct from the in vitro activities demonstrated. The isolation and functional characterisation of VvCCD4a and VvCCD4b identify two additional CCDs that are functional in grapevine. Taken together, our results indicate that the three CCDs are under various levels of control that include gene expression (spatial and temporal), substrate specificity and compartmentalisation that act individually and/or co-ordinately to maintain carotenoid and volatile apocarotenoid levels in plants. Altering the expression of VvCCD1 in a transgenic grapevine population illustrated the divergence between the in vitro enzyme activity and the in planta activity of this enzyme, thereby contributing to the efforts to understand how enzymatic degradation of carotenoids involved in photosynthesis occurs. The identification and functional characterisation of VvCCD4a and VvCCD4b suggest that these enzymes are primarily responsible for catalysing the cleavage of plastidial carotenoids.


Metabolism to a response pathway selective retinoid ligand during axial pattern formation.
We report identification of 9-cis-4-oxo-retinoic acid (9-cis-4-oxo-RA) as an in vivo retinoid metabolite in Xenopus embryos. 9-Cis-4-oxo-RA bound receptors (RARs) alpha, beta, and gamma as well as retinoid X receptors (RXRs) alpha, beta, and gamma in vitro. However, this retinoid displayed differential RXR activation depending on the response pathway used. Although it failed to activate RXRs in RXR homodimers, it activated RXRs and RARs synergistically in RAR-RXR heterodimers. 9-Cis-4-oxo-RA thus acted as a dimer-specific agonist. Considering that RAR-RXR heterodimers are major functional units involved in transducing retinoid signals during embryogenesis and that 9-cis-4-oxo-RA displayed high potency for modulating axial pattern formation in Xenopus, metabolism to 9-cis-4-oxo-RA may provide a mechanism to target retinoid action to this and other RAR-RXR heterodimer-mediated processes.


Synaptic transmission in submucosal ganglia of guinea pig distal colon.
Intracellular electrical recording was used to investigate synaptic behavior of ganglion cells in the neural networks of the submucosal plexus of the guinea pig distal colon. Fast excitatory postsynaptic potentials (EPSPs), mediated by nicotinic receptors, were found in all S/type 1 neurons, 70% of AH/type 2, 75% of type 3, and 95% of type 4 neurons. Slow EPSPs were characterized by membrane depolarization, increased input resistance, enhanced action potential discharge, and suppression of hyperpolarizing afterpotentials in 64% of the S/type 1 neurons, 74% of AH/type 2, 31% of type 3, and 70% of type 4 neurons. Micropressure application of acetylcholine evoked a two-component depolarizing response consisting of an initial transient with decreased input resistance followed by a prolonged depolarization associated with increased input resistance. The transient response was suppressed by nicotinic-blocking drugs. Muscarinic antagonists suppressed the prolonged response. Acetylcholine acted also at presynaptic muscarinic receptors to suppress stimulus-evoked fast EPSPs. No stimulus-evoked inhibitory synaptic potentials were observed. Norepinephrine, applied by microejection, acted at alpha 2-adrenoceptors to hyperpolarize the membrane potential in association with decreased neuronal input resistance.


"Social justice is a dream": Tensions and contradictions in nursing education.
The purpose of this study was to explore nurse educators' conceptualizations of social justice in theory courses. The findings contextualize the role of nurse educators in promoting social justice among future health care providers and the relevance of their perspectives on social justice. This descriptive qualitative study was completed utilizing constructivist grounded theory methods. I interviewed 28 nurse educators teaching theory courses in Baccalaureate nursing programs on the West coast of the United States. Initial and focused codes were constructed from interview transcripts to understand and contextualize statements about social justice. Participants' conceptualizations of social justice include equity, equality, self-awareness, withholding judgment, and taking action. Notable differences emerged along racial lines and, less so, in relation to educational background and nursing specialty. This study highlights areas of concern with respect to how nurse educators enact the claim that social justice is a core professional nursing value. The findings call attention to tensions and contradictions as individuals navigate the landscape of nursing with limited structural and institutional effort.


Designing Polymeric Interphases for Stable Lithium Metal Deposition.
Reactive metals are known to electrodeposit with irregular morphological features on planar substrates. A growing body of work suggest that multiple variables: composition, mechanics, structure, ion transport properties, reductive stability, and interfacial energy of interphases, formed either spontaneously or by design on the metal electrode play important but differentiated roles in regulating these morphologies. We examine the effect of fluorinated thermoset polymer coatings on Li deposition by means of experiment and theoretical linear stability analysis. By tuning the chemistry of the polymer backbone and side chains, we investigate how physical and mechanical properties of polymeric interphases influence Li electrodeposit morphology. It is found that an interplay between elasticity and diffusivity leads to an optimum interphase thickness and that higher interfacial energy augments elastic stresses at a metal electrode to prevent out-of-plane deposition. These findings are explained using linear stability analysis of electrodeposition and provide guidelines for designing polymer interphases to stabilize metal anodes in rechargeable batteries.


Accurate gestational dating.
Gestational age by four ultrasonic parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) was calculated for 210 normal obstetric patients divided into four gestational age groups based on time of first ultrasound examination. Accuracy of the calculations was determined by comparison of each technique and a simple arithmetic average of the four techniques to the gestational age calculated from the Dubowitz examination of the neonate after delivery. The analysis indicated that each ultrasonic technique has certain advantages and disadvantages, but that the simple arithmetic average of the four techniques had the lowest systematic and random error.


Sch-28080 inhibits bafilomycin-sensitive H+ secretion in turtle bladder independently of luminal [K+].
To explore the possible contribution of an H-K-adenosine-triphosphatase (H-K-ATPase) to H+ secretion (JH) in the isolated turtle bladder, we measured electrogenic JH (JeH) as short-circuit current and total JH (JTH) by pH stat titration in the presence of ouabain at different ambient K+ concentration ([K+]) and during luminal addition of a known gastric H-K-ATPase inhibitor, Schering (Sch)-28080. JH was not reduced by decreasing ambient [K+] to undetectable or very low levels (< 0.05 mM by atomic absorption) and luminal BaCl2 addition to further reduce local [K+] at the apical membrane. These K(+)-removal studies indicate that H+ transport is not coupled to countertransport of K+. JTH did not exceed JeH at any point: in K(+)-free solutions JTH was 0.73 +/- 0.05, and JeH was 0.95 +/- 0.08 mumol/h; in standard (3.5 mM) K+ solutions JTH was 0.72 +/- 0.05 and JeH 0.98 +/- 0.06 mumol/h; in high (118 mM) K+ solutions JTH was 0.65 +/- 0.07 and JeH 0.94 +/- 0.08 mumol/h. Sch-28080 caused a rapid inhibition of JH, with similar half-maximal inhibitory concentrations (IC50) in K(+)-free, standard [K+], and high [K+] solutions. Bafilomycin inhibited JeH and JTH with an IC50 of approximately 100 nM. The observed non-potassium-competitive inhibition of JH by Sch-28080 and the bafilomycin sensitivity distinguish the H-ATPase of the turtle bladder from the gastric H-K-ATPase. The rapidity of the inhibition by Sch-28080 suggests that it acts at an accessible luminal site of the ATPase.


[Significance of studies on cyclic nucleotide metabolism for practical medicine].
Based on the results of own studies and data available in literature the evidence is given on peculiarities of determination and estimation criteria for the content of cyclic nucleotides in people. Changes in the metabolism of these substances and their pathogenic role are considered for a large number of diseases. Pharmacotherapeutic aspects are described, in particular regulation of enzymes taking part in the metabolism of cyclic nucleotides. The data are presented pertaining to the clinical application of phosphodiesterase inhibitors in oncology, in diseases of the cardiovascular system, respiratory system and in neuropathology. Approaches to a selective modification of cyclic nucleotides metabolism in clinical practice are considered.


Rhinoviruses delayed the circulation of the pandemic influenza A (H1N1) 2009 virus in France.
In contrast to the experience in other European countries, the onset of the A(H1N1)2009 influenza virus epidemic was unexpectedly slow in France during the first part of autumn 2009. Our objective was to test the hypothesis that intense circulation of rhinoviruses might have reduced the probability of infection by A(H1N1)2009 virus at the beginning of autumn 2009. Systematic analysis for the detection of A(H1N1)2009 (H1N1) and human rhinovirus (HRV) was performed by RT-PCR from week 36 to week 48 on respiratory samples sent to the diagnostic laboratory by the paediatric hospital (n = 2121). Retrospective analysis of the obtained data, using 2 x 2 contingency tables with Fisher's exact test, revealed evidence of an inverse relationship between HRV and H1N1 detection. Between weeks 36 and 48 of 2009, both HRV and H1N1 were detected but in different time frames. HRV dispersed widely during early September, peaking at the end of the month, whereas the H1N1 epidemic began during mid-October and was still active at the end of this survey. During the co-circulation period of these two respiratory viruses (weeks 43-46), HRV detection appeared to reduce the likelihood of H1N1 detection in the same sample (OR = 0.08-0.24 p <0.0001). These results support the hypothesis that HRV infections can reduce the probability of A(H1N1) infection. This viral interference between respiratory viruses could have affected the spread of the H1N1 viruses and delayed the influenza pandemic at the beginning of autumn in France.


Rheumatoid arthritis-associated polymorphisms are not protective against Alzheimer's disease.
Rheumatoid arthritis (RA) and Alzheimer's disease (AD) are inversely associated. To test the hypothesis that genetic elements associated with increased RA risk are associated with decreased AD risk, we evaluated RA genetic risk factors recently identified in genome-wide association studies (GWAS) for their association with AD in a two-stage, case-control analysis. In our Stage 1 analysis of ~800 AD and ~1,200 non-AD individuals, three of seventeen RA-associated SNPs were nominally associated with AD (p < 0.05) with one SNP, rs2837960, retaining significance after correction for multiple testing (p = 0.03). The rs2837960_G (minor) allele, which is associated with increased RA risk, was associated with increased AD risk. Analysis of these three SNPs in a Stage 2 population, consisting of ~1,100 AD and ~2,600 non-AD individuals, did not confirm their association with AD. Analysis of Stage 1 and 2 combined suggested that rs2837960 shows a trend for association with AD. When the Stage 2 population was age-matched for the Stage 1 population, rs2837960 exhibited a non-significant trend with AD. Combined analysis of Stage 1 and the age-matched Stage 2 subset showed a significant association of rs2837960 with AD (p = 0.002, OR 1.24) that retained significance following correction for age, sex and APOE (p = 0.02, OR = 1.20). Rs2837960 is near BACE2, which encodes an aspartic protease capable of processing the AD-associated amyloid precursor protein. Testing for an association between rs2837960 and the expression of BACE2 isoforms in human brain, we observed a trend between rs2837960 and the total expression of BACE2 and the expression of a BACE2 transcript lacking exon 7 (p = 0.07 and 0.10, respectively). RA-associated SNPs are generally not associated with AD. Moreover, rs2837960_G is associated with increased risk of both RA and, in individuals less than 80 years of age, with AD. Overall, these results contest the hypothesis that genetic variants associated with RA confer protection against AD. Further investigation of rs2837960 is necessary to elucidate the mechanism by which rs2837960 contributes to both AD and RA risk, likely via modulation of BACE2 expression.


Ca2+ uptake by the endoplasmic reticulum Ca2+-ATPase in rat microvascular endothelial cells.
In non-excitable cells, many agonists increase the intracellular Ca(2+) concentration ([Ca(2+)](i)) by inducing an inositol 1,4,5-trisphosphate (IP(3))-mediated Ca(2+) release from the intracellular stores. Ca(2+) influx from the extracellular medium may then sustain the Ca(2+) signal. [Ca(2+)](i) recovers its resting level as a consequence of Ca(2+)-removing mechanisms, i.e. plasma-membrane Ca(2+)-ATPase (PMCA) pump, Na(+)/Ca(2+) exchanger (NCX) and sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump. In a study performed in pancreatic acinar cells, evidence has been provided suggesting that, during the decay phase of the agonist-evoked Ca(2+) transients, the Ca(2+) concentration within the intracellular stores remains essentially constant [Mogami, Tepikin and Petersen (1998) EMBO J. 17, 435-442]. It was therefore hypothesized that, in such a situation, intracellular Ca(2+) is not only picked up by the SERCA pump, but is also newly released through IP(3)-sensitive Ca(2+) channels, with the balance between these two processes being approximately null. The main aim of the present work was to test this hypothesis by a different experimental approach. Using cardiac microvascular endothelial cells, we found that inhibition of the SERCA pump has no effect on the time course of agonist-evoked Ca(2+) transients. This result was not due to a low capacity of the SERCA pump since, after agonist removal, this pump proved to be very powerful in clearing the excess of intracellular Ca(2+). We showed further that: (i) in order to avoid a rapid removal of Ca(2+) by the SERCA pump, continuous IP(3) production appears to be required throughout all of the decay phase of the Ca(2+) transient; and (ii) Ca(2+) picked up by the SERCA pump can be fully and immediately released by agonist application. All these results support the model of Mogami, Tepikin and Petersen [(1998) EMBO J. 17, 435-442]. Since the SERCA pump did not appear to be involved in shaping the decay phase of the agonist-evoked Ca(2+) transient, we inhibited the PMCA pump with carboxyeosin, and NCX with benzamil and by removing extracellular Na(+). The results indicate that, during the decay phase of the agonist-evoked Ca(2+) transient, the intracellular Ca(2+) is removed by both the PMCA pump and NCX. Finally, we provide evidence indicating that mitochondria have no role in clearing intracellular Ca(2+) during agonist-evoked Ca(2+) transients.


Expression of neoplasia-related proteins of chemically transformed HuT fibroblasts in human osteosarcoma HOS fibroblasts and modulation of actin expression upon elevation of tumorigenic potential.
Two sets of abundant cytoplasmic transformation-specific polypeptides, p788/p789 and p219/p220, have been identified by comparing in vitro-transformed human fibroblasts with diploid human fibroblasts. These polypeptides are also expressed by the human fibrosarcoma and osteosarcoma cell lines HT1080 the human fibrosarcoma and osteosarcoma cell lines HT1080 and HOS, respectively. HOS cells, however, synthesize only one of the two electrophoretic forms of each marker set, p789 and p219, at greatly reduced rates compared to the rates of synthesis found for HT1080 cells and the in vitro-transformed cell lines. Induction of expression of these neoplastic marker polypeptides is independent of the activation of a transforming gene that will induce focus formation in confluent mouse 3T3 cell monolayers. Activation of the met oncogene in MNNG-HOS cells and simultaneous elevation of tumorigenic potential did not lead to a significant change in the rate of the 600 most abundant polypeptide species with the exception of one of the two cytoplasmic actin polypeptides. While the normal ratio of beta-to gamma-actin which is approximately 2:1 was expressed in "untransformed" HOS cells, MNNG-HOS cells synthesized 50% less beta-actin resulting in a 1:1 ratio of beta-actin to gamma-actin. Our finding here, together with our previous characterization of the human beta-actin gene, leads us to predict that one of two functional beta-actin genes expressed in HOS cells has been inactivated in MNNG-HOS cells by either a regulatory or structural gene mutation.


A carboxy-terminal truncation of human alpha-galactosidase A in a heterozygous female with Fabry disease and modification of the enzymatic activity by the carboxy-terminal domain. Increased, reduced, or absent enzyme activity depending on number of amino acid residues deleted.
Fabry disease is an X-linked disorder of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A (alpha-Gal A). We identified a novel mutation of alpha-Gal A gene in a family with Fabry disease, which converted a tyrosine at codon 365 to a stop and resulted in a truncation of the carboxy (C) terminus by 65 amino acid (AA) residues. In a heterozygote of this family, although the mutant and normal alleles were equally transcribed in cultured fibroblasts, lymphocyte alpha-Gal A activity was approximately 30% of the normal control and severe clinical symptoms were apparent. COS-1 cells transfected with this mutant cDNA showed a complete loss of its enzymatic activity. Furthermore, those cotransfected with mutant and wildtype cDNAs showed a lower alpha-Gal A activity than those with wild type alone (approximately 30% of wild type alone), which suggested the dominant negative effect of this mutation and implied the importance of the C terminus for its activity. Thus, we generated mutant cDNAs with various deletion of the C terminus, and analyzed. Unexpectedly, alpha-Gal A activity was enhanced by up to sixfold compared with wild-type when from 2 to 10 AA residues were deleted. In contrast, deletion of 12 or more AA acid residues resulted in a complete loss of enzyme activity. Our data suggest that the C-terminal region of alpha-Gal A plays an important role in the regulation of its enzyme activity.


Altered evoked low-frequency connectivity from SI to ACC following nerve injury in rats.
Objective. Despite decades of research on central processing of pain, there are still several unanswered questions, in particular regarding the brain regions that may contribute to this alerting sensation. Since it is generally accepted that more than one cortical area is responsible for pain processing, there is an increasing focus on the interaction between areas known to be involved.Approach. In this study, we aimed to investigate the bidirectional information flow from the primary somatosensory cortex (SI) to the anterior cingulate cortex (ACC) in an animal model of neuropathic pain.19 rats (nine controls and ten intervention) had an intracortical electrode implanted with six pins in SI and six pins in ACC, and a cuff stimulation electrode around the sciatic nerve. The intervention rats were subjected to the spared nerve injury (SNI) after baseline recordings. Electrical stimulation at three intensities of both noxious and non-noxious stimulation was used to record electrically evoked cortical potentials. To investigate information flow, two connectivity measures were used: phase lag index (PLI) and granger prediction (GP). The rats were anesthetized during the entire study.Main results. Immediately after the intervention (<5 min after intervention), the high frequency (γandγ+) PLI was significantly decreased compared to controls. In the last recording cycle (3-4 h after intervention), the GP increased consistently in the intervention group. Peripheral nerve injury, as a model of neuropathic pain, resulted in an immediate decrease in information flow between SI and ACC, possibly due to decreased sensory input from the injured nerve. Hours after injury, the connectivity between SI and ACC increased, likely indicating hypersensitivity of this pathway.Significance. We have shown that both a directed and non-directed connectivity between SI and ACC approach can be used to show the acute changes resulting from the SNI model.


The impact of Mississippi's mandatory delay law on abortions and births.
Beginning August 8, 1992, a woman in the state of Mississippi had to wait 24 hours after in-person receipt of state-mandated information regarding abortion and birth complications, fetal development, and alternatives to abortion before an abortion could be performed. To analyze the effect of the law on the abortion and birth rates of Mississippi residents. A retrospective analysis of abortion and birth rates before and after the law in Mississippi as contrasted with abortion and birth rates in 2 comparison states, Georgia and South Carolina. Neither Georgia nor South Carolina enforced a mandatory delay law, but both states began enforcement of parental notification statutes during the study period. Female residents of reproductive age in Mississippi, Georgia, and South Carolina between 1989 and 1994. We compared birth rates, abortion rates, the percentage of late abortions, and the percentage of abortions performed outside the state of residence for all women and then by age and race before and after August 1992 among women of Mississippi, Georgia, and South Carolina. We found that rate ratios (RRs) of resident abortion rates (rate after law implementation/rate before law implementation) declined 12% more in Mississippi than in South Carolina (95% confidence interval [CI], 8%-15%) and 14% more in Mississippi than in Georgia (95% CI, 10%-17%) in the 12 months after the law went into effect. Rate ratios for white adults declined 22% more in Mississippi than in South Carolina (95% CI, 17%-27%) and 20% more in Mississippi than in Georgia (95% CI, 15%-25%). Changes among nonwhite adults and white teens were more modest but also statistically significant (P<.05). For all women, RRs of the percentage of abortions performed after 12 weeks' gestation increased 39% more in Mississippi than in either South Carolina or Georgia (P<.05); the increase in the percentage of abortions after 12 weeks' gestation was observed for white and non-white adults (P<.05). We also show that the percentage of abortions performed out of state increased 42% more among women in Mississippi relative to women in South Carolina after the law (95% CI, 34%-50%). The timing of the decline in abortion rates in Mississippi, the lack of similar declines in comparison states, the rise in percentage of late abortions and abortions performed out of state and the apparent completeness of abortion reports suggest that Mississippi's mandatory delay statute was responsible for a decline in abortion rates and an increase in abortions performed later in pregnancy among residents of Mississippi. The effect of delay laws in other states will likely depend on whether statutes require 2 separate visits to the abortion provider (ie, clinics, hospitals, or physicians' offices where abortions are performed) and the availability of abortion services.


Integrated microarray analysis provided novel insights to the pathogenesis of glaucoma.
Glaucoma is characterized as a visual field defect, which is the second most common cause of blindness. The present study performed an integrated analysis of microarray studies of glaucoma derived from Gene Expression Omnibus (GEO). Following the identification of the differentially expressed genes (DEGs) in glaucoma compared with normal control (NC) tissues, the functional annotation, glaucoma‑specific protein‑protein interaction (PPI) network and transcriptional regulatory network constructions were performed. The acute intraocular pressure (IOP) elevation rat models were established and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed for DEGs expression confirmation. Three datasets were downloaded from GEO. A total of 97 DEGs, 82 upregulated and 15 downregulated were identified in glaucoma compared with NC groups with false discovery rate <0.05. Response to virus and immune response were two significantly enriched GO terms in glaucoma. Valine, leucine and isoleucine degradation was a significantly enriched pathway of DEGs in glaucoma. According to the PPI network, HDAC1, HBN, UBR4 and PDK1 were hub proteins in glaucoma. FOXD3, HNF‑4 and AP‑1 were the three transcription factors (TFs) derived from top 10 TFs which covered the majority of downstream DEGs in glaucoma. Based on the RT‑qPCR results, the expression levels of 3 DEGs, raftlin, lipid raft linker 1 (RFTN1), PBX homeobox 1 (PBX1), HDAC1 were significantly upregulated and the expression of GEM was significantly downregulated in acute IOP elevation rat model at the first and fifth day. These four DEGs had the same expression pattern with our integrated analysis. Therefore, the current study concluded that 6 DEGs, including HEPH, SELENBP1, RFTN1, ID1, HDAC‑1 and PBX1 and three TFs, including FOXD3, HNF‑4 and AP‑1 may be involved with the pathogenesis of glaucoma. The findings of the current study may improve diagnosis and drug design for glaucoma.


Anti-inflammatory effects of intramammary infusions of glycyrrhizin in lactating cows with mastitis caused by coagulase-negative staphylococci.
To determine the anti-inflammatory effects of glycyrrhizin (GL) in lactating cows with mastitis attributable to naturally occurring infection with coagulase-negative staphylococci (CNS). 12 lactating Holstein cows with mastitis attributable to infection with CNS and 2 healthy cows without mastitis. Clinical signs, number of bacteria in milk, somatic cell count (SCC) in milk, concentrations of alpha-lactalbumin and lactoferrin in milk, and concentration of histamine in milk were investigated before and after intramammary infusion of GL (6 cows) or antimicrobials (6 cows). Glands of 2 healthy cows were infused with staphylococcal enterotoxin; milk leukocytes were then harvested and incubated with various doses of GL. In cows infected with CNS that had a low bacterial concentration in milk, infusion of GL alone resulted in significant improvements in swelling, firmness of glands, and number of clots in milk, and it decreased the SCC, but not significantly. Percentage of neutrophils decreased significantly (to < 30%) by 2 days after infusion. Use of lactoferrin as a marker of inflammation in mammary glands revealed a decrease in concentrations, whereas use of alpha-lactalbumin as a marker of recovery for mammary glands revealed significant increases in concentrations in the GL-infused group. Accompanying these anti-inflammatory effects, a decrease in the concentration of histamine in milk was observed in the GL-infused group. Glycyrrhizin decreased histamine production by milk leukocytes in a concentration-dependent manner. Infusion of GL may regulate intramammary inflammation through modulation of inflammatory mediators such as histamine.