Strategies and approaches in oral disease prevention and health promotion.
Oral health is an important element of general health and well-being. Although largely preventable, many people across the world still suffer unnecessarily from the pain and discomfort associated with oral diseases. In addition, the costs of dental treatment are high, both to the individual and to society. Effective evidence-based preventive approaches are needed to address this major public health problem. The aim of this paper is to outline public health strategies to promote oral health and reduce inequalities. An extensive collection of public health policy documents produced by WHO are reviewed to guide the development of oral health strategies. In addition a range of Cochrane and other systematic reviews assessing the evidence base for oral health interventions are summarized. Public health strategies should tackle the underlying social determinants of oral health through the adoption of a common risk approach. Isolated interventions which merely focus on changing oral health behaviours will not achieve sustainable improvements in oral health. Radical public health action on the conditions which determine unhealthy behaviours across the population is needed rather than relying solely on the high-risk approach. Based upon the Ottawa Charter, a range of complementary strategies can be implemented in partnership with relevant local, national and international agencies. At the core of this public health approach is the need to empower local communities to become actively involved in efforts to promote their oral health.


Alkaline lipase in rat intestinal mucosa: physiological parameters.
The present studies describe an alkaline active lipase in the rat intestinal mucosa. Alkaline lipase activity was determined using a glyceryl tri[14C]oleate emulsion at pH 8.0. Subcellular fractions were prepared from mucosal homogenates by differential centrifugation. Cells from villus to crypt were sequentially released using citrate and EDTA buffer. The enzyme was found to be most active in the proximal quarter of the intestine and in villus tips. Most of the activity was found in the cytosolic fraction. Bile salts stimulated the enzyme activity threefold. The presence of both Ca2+ and taurocholate was essential for optimal activity. Mucosal activity was greatly reduced on intraduodenal glyceryl trioleate infusion. Activity was restored when phosphatidylcholine was added to the glyceryl trioleate infusion. The fact that mucosal lipase has its greatest activity in the villus tips of the proximal intestine and in cytosol suggests that it may play an important role in mucosal glyceryltrioleate metabolism.


Mobility and low contrast trip hazard avoidance using augmented depth.
We evaluated a novel visual representation for current and near-term prosthetic vision. Augmented depth emphasizes ground obstacles and floor-wall boundaries in a depth-based visual representation. This is achieved by artificially increasing contrast between obstacles and the ground surface via a novel ground plane extraction algorithm specifically designed to preserve low-contrast ground-surface boundaries. The effectiveness of augmented depth was examined in human mobility trials compared against standard intensity-based (Intensity), depth-based (Depth) and random (Random) visual representations. Eight participants with normal vision used simulated prosthetic vision with 20 phosphenes and eight perceivable brightness levels to traverse a course with randomly placed small and low-contrast obstacles on the ground. The number of collisions was significantly reduced using augmented depth, compared with intensity, depth and random representations (48%, 44% and 72% less collisions, respectively). These results indicate that augmented depth may enable safe mobility in the presence of low-contrast obstacles with current and near-term implants. This is the first demonstration that an augmentation of the scene ensuring key objects are visible may provide better outcomes for prosthetic vision.


The bat community of Haiti and evidence for its long-term persistence at high elevations.
Accurate accounts of both living and fossil mammal communities are critical for creating biodiversity inventories and understanding patterns of changing species diversity through time. We combined data from from14 new fossil localities with literature accounts and museum records to document the bat biodiversity of Haiti through time. We also report an assemblage of late-Holocene (1600-600 Cal BP) bat fossils from a montane cave (Trouing Jean Paul, ~1825m) in southern Haiti. The nearly 3000 chiropteran fossils from Trouing Jean Paul represent 15 species of bats including nine species endemic to the Caribbean islands. The fossil bat assemblage from Trouing Jean Paul is dominated by species still found on Hispaniola (15 of 15 species), much as with the fossil bird assemblage from the same locality (22 of 23 species). Thus, both groups of volant vertebrates demonstrate long-term resilience, at least at high elevations, to the past 16 centuries of human presence on the island.


Impact of an Outdoor Smoking Ban at Secondary Schools on Cigarettes, E-Cigarettes and Water Pipe Use among Adolescents: An 18-Month Follow-Up.
Abstract: The effectiveness of outdoor smoking bans on smoking behavior among adolescents remains inconclusive. This study evaluates the long-term impact of outdoor school ground smoking bans among adolescents at secondary schools on the use of conventional cigarettes, e-cigarettes (with/without nicotine) and water pipes. Outdoor smoking bans at 19 Dutch secondary schools were evaluated using a quasi-experimental design. Data on 7733 adolescents were obtained at baseline, and at 6 and 18-month follow-up. The impact of outdoor smoking bans on 'ever use of conventional cigarettes', 'smoking onset', 'ever use of e-cigarette with nicotine', 'e-cigarette without nicotine', and 'water pipe' was measured. Multilevel logistic regression analysis was used. At schools with a ban, implementation fidelity was checked. At schools where a ban was implemented, at 18-month follow-up more adolescents had started smoking compared to the control condition. No effect of implementation of the ban was found for smoking prevalence, e-cigarettes with/without nicotine, and water pipe use. Implementation fidelity was sufficient. No long-term effects were found of an outdoor smoking ban, except for smoking onset. The ban might cause a reversal effect when schools encounter difficulties with its enforcement or when adolescents still see others smoking. Additional research is required with a longer follow-up than 18 months.


Electromyographic response is altered during robotic surgical training with augmented feedback.
There is a growing prevalence of robotic systems for surgical laparoscopy. We previously developed quantitative measures to assess robotic surgical proficiency, and used augmented feedback to enhance training to reduce applied grip force and increase speed. However, there is also a need to understand the physiological demands of the surgeon during robotic surgery, and if training can reduce these demands. Therefore, the goal of this study was to use clinical biomechanical techniques via electromyography (EMG) to investigate the effects of real-time augmented visual feedback during short-term training on muscular activation and fatigue. Twenty novices were trained in three inanimate surgical tasks with the da Vinci Surgical System. Subjects were divided into five feedback groups (speed, relative phase, grip force, video, and control). Time- and frequency-domain EMG measures were obtained before and after training. Surgical training decreased muscle work as found from mean EMG and EMG envelopes. Grip force feedback further reduced average and total muscle work, while speed feedback increased average muscle work and decreased total muscle work. Training also increased the median frequency response as a result of increased speed and/or reduced fatigue during each task. More diverse motor units were recruited as revealed by increases in the frequency bandwidth post-training. We demonstrated that clinical biomechanics using EMG analysis can help to better understand the effects of training for robotic surgery. Real-time augmented feedback during training can further reduce physiological demands. Future studies will investigate other means of feedback such as biofeedback of EMG during robotic surgery training.


Response to peginterferon alfa-2a (40KD) in HBeAg-negative CHB: on-treatment kinetics of HBsAg serum levels vary by HBV genotype.
We investigated whether HBV genotype influences on-treatment HBsAg kinetics and/or the end-of-treatment HBsAg levels associated with long-term virological response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a±lamivudine in the Phase III trial. All patients (n=230) who participated in long-term follow-up were included according to the availability of HBsAg level measurements. Long-term virological response was defined as HBV DNA ≤ 10,000cp/ml (1786IU/ml) at 5 years post-treatment. Genotype-specific end-of-treatment HBsAg levels associated with long-term virological response (identified by ROC analysis) were assessed in 199 patients with HBsAg measurements available at baseline and end-of-treatment. HBsAg kinetics according to genotype and long-term virological response were investigated in the 117 patients with additional samples available at weeks 12, 24, and 72. Baseline HBsAg levels were significantly higher for A than B, C, and D genotypes (p<0.05). On-treatment HBsAg kinetics varied according to HBV genotype. The difference between responders and non-responders was greatest for genotype A from weeks 12-24; for genotypes B and D from baseline to week 12; there was no significant difference over any timeframe for genotype C. High positive predictive values for long-term virological response could be obtained by applying end-of-treatment genotype-specific cut-offs: 75%, 47%, 71%, and 75% for genotypes A (<400IU/ml), B (<50IU/ml), C (<75IU/ml), and D (<1000IU/ml), respectively. On-treatment HBsAg kinetics vary between HBV genotypes. Genotype-specific monitoring timeframes and end-of-treatment thresholds could ameliorate response-guided treatment of HBeAg-negative chronic hepatitis B.


Endometrial thickness in women with ovulatory dysfunction.
This study is designed to evaluate the relationship between endometrial thickness and clinical/biochemical parameters in women with chronic anovulation. One hundred and twenty women with ovulatory dysfunction were prospective included, endometrial thickness and endocrine and metabolic parameters were measured. The interval between the examination day and the day of the most recent menstrual bleeding (the anovulatory interval) for the studied subject was an average of 145 ± 186 days. The endometrial thickness averaged 7.1 ± 3.2 mm. Correlation analyses revealed that the endometrial thickness was positively correlated with body mass index but was not correlated with age, serum androgens, or estradiol (E2) levels. We further classified the subjects into two groups based on endometrial thickness: Group A, endometrial thickness <7 mm and Group B, endometrial thickness ≥7 mm. The anovulatory interval, follicle-stimulating hormone, luteinizing hormone, E2 and androgen levels were not significantly different between Groups A and B. Group B had higher body weight and more risk for metabolic syndrome. We concluded that endometrial thickness in women with ovulatory dysfunction is positively correlated with body weight status but is not correlated with serum androgens or E2 levels.


[Evaluation of skin prick tests and serum concentration of antigen-specific immunoglobulin E in patients with atopic dermatitis sensitive to airborne allergens in relation to the type of allergens and age of patients].
Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with sensitivity to common airborne allergens. The aim of the study was to evaluate the immediate type of immunological reaction initiated by main types of airborne allergens in the pathomechanism of atopic dermatitis in relation to the age of patients. 529 patients with AD aged (0.5-60 years) who fulfilled basic Hanifin and Rajka criteria and 60 healthy volunteers in the control group were investigated. In order to IgE-mediated allergy to common airborne allergens skin prick tests (SPT) were performed (26 airborne allergens) and concentration of serum antigen specific IgE (asIgE) was measured. Our results indicated increasing prevalence to sensitisation to airborne allergens in patients with AD in relation to the age of these patients (age 0.5-4--17 cases; 5-12 years--127 cases; 13-18 years--88 cases; above 18 of age--173 cases). The sensitisation to grass pollen and house dust mite allergens was predominant. We conclude, that predominance to sensitization to airborne allergens tends to increase with the age of patients.


[Anthropomorphic features of patients with tuberculosis of the prostate].
Modern TB patient has lost the physical appearance (habitus phtisicus) typical for the previous years. Moreover, patients with different tuberculosis localizations also have different anthropomorphic characteristics. To determine anthropomorphic characteristics of patients with tuberculosis of the prostate, several parameters were compared between 95 male patients with pulmonary tuberculosis and 49 patients with prostatic tuberculosis. Compared to pulmonary tuberculosis patients, patients with prostatic tuberculosis were significantly more likely to be overweight and have greater waist circumference. Among patients with pulmonary tuberculosis, there were significantly more people of short or very tall stature, while patients with prostatic tuberculosis, on the contrary, were significantly more likely to be of average height (166-180 cm). The findings regarding body structure of a patient with tuberculosis of the prostate (fat stocky man) could possibly reflect the presence of the metabolic syndrome that may account for the greater susceptibility to urogenital infections.


DFT/NEGF study of discrete dopants in Si/III-V 3D FET.
In this work, electron densities around dopants in Si and GaAs have been calculated using density functional theory (DFT) calculations. These extracted densities have been used to describe dopants in an in-house non-equilibrium Green functions device simulator. The transfer characteristics of nanowire gate all around field effect transistor have been calculated using DFT electron densities. These transport calculations were compared with those using a point charge model of the dopant. The dopants are located in the middle of the channel of the device. Specifically, DFT calculations of a 512 atom Si supercell with a single impurity atom have been carried out, both phosphorous and boron atoms have been used as donor and acceptor impurities respectively. The calculations were repeated on a gallium arsenide supercell, where the silicon atom substituted gallium and arsenide to act as donor and acceptor respectively. We found that for donors and acceptors, the DFT charge distribution extends similarly in both materials. In addition, the relaxed structure produces a 50% larger spread of electronic charge as compared with unrelaxed Si and GaAs. The extracted current voltage characteristics of the devices are altered significantly using the charge density obtained by DFT. At 0.7 V the current in Si is 20% larger using the DFT charge density compared to the point charge model for donors. Whereas the current using the point charge model in GaAs is 2.5 times larger than the distributed charge. Devices exhibit substantial tunnelling currents for donors and acceptors irrespective of the model of the dopant considered. In GaAs, this was 76% using a point charge and 78% using the distributed charge when using a donor; 61% and 68% in Si respectively. The tunnelling current using acceptors for Si was 100% and 99% using GaAs for both models.


Analysis of bacterial communities in rhizosphere soil of continuously cropped healthy and diseased konjac.
The bacterial community and diversity in healthy and diseased konjac rhizosphere soils with different ages of continuous cropping were investigated using next-generation sequencing. The results demonstrated that the number of years of continuous cropping significantly altered soil bacterial community and diversity. Soil bacterial Shannon diversity index and Chao 1 index decreased with the increasing cropping years of konjac. After 1 year of cropping, the soil exhibited the highest bacterial relative abundance and diversity. Of the 44 bacterial genera (relative abundance ratio of genera greater than 0.3%), 14 were significantly affected by the duration of continuous cropping and plant status. With increasing continuous cropping, Alicyclobacillus decreased, while Achromobacter, Lactobacillus, Kaistobacter, Rhodoplanes increased after 3 years continuous cropping. Continuous cropping altered the structure and composition of the soil bacterial community, which led to the reduction in the beneficial bacteria and multiplication of harmful bacteria. These results will improve our understanding of soil microbial community regulation and soil health maintenance in konjac farm systems.


Lewy body-free nigral degeneration--a case report.
A 70-year-old Japanese woman developed progressive, dopa-responsive parkinsonism consisting of akinesia, resting tremor, rigidity, and postural instability. Neuropathological examination revealed a marked loss of nigral neurons, but no Lewy bodies (LBs) were observed. Lewy bodies were also absent from their usual site, with the exception of a small number seen in the dorsal motor nucleus of the vagus nerve (DVN) and sympathetic ganglion. We propose that our case and several similar reported cases represent Lewy body-free nigral degeneration.


[Nutrition value of wild-growing fruits from mountain Dagestan and its safety after fast freezing and cold storage].
Results of research of mineral composition, content of vitamin C and P, titrable acids, pectinaceous and phenol substances in fresh, fast-frozen (t=-30 °C), and also stored within 3 and 9 months (t=-18 °C) fruits of wild-growing blackberry, cornel, medlar and sea-buckthorn are presented in article. Determination of mineral composition was carried out by flame atomic absorption photometry, vitamin C and pectinaceous substances -by titirimetric methods, phenolic substances and vitamin P - by colorimetric methods. Vitamin C content was minimal in fresh fruits of cornel (6.9±0.3 mg%), amounted to 21.7-32.0 mg% in the fruits of blackberries and medlar and reached 180.1±7.2 mg% in the fruit of sea-buckthorn. Vitamin P concentration ranged from 34.9 (sea-buckthorn) to 180.0 mg% (cornel). Berries of a cornel contained also the greatest number of titrable acids (33.2±1.3 g/dm3), phenolic compounds (243.0±4.8 mg%) and pectinaceous substances (2.91±0.08%). The most significant content of potassium (521±15.6 mg%), calcium (133.2±5.2 mg%), magnesium (62.4±2.5 mg%) and iron (2.81±0.05 mg%) was revealed in medlar fruits. Consumption of 100 g of the studied fruits provides daily requirements of a human body, depending on a species of wild plants: in calcium -for 2-13.3%, potassium - for 7.0-20.8%, magnesium - for 8.1-15.6%, iron - for 5.9-19.2% and in vitamin C - from 5.8-24.6 to 145.7% in the case of sea buckthorn. The applied processing method of conservation - fast freezing (t=-30 °С) of fruits and their long storage (t=-18 °С) is the effective way ensuring high safety of nutrients in them. In the studied berries after 9-months cold storage the safety of vitamin C varied ranging from 55.7 (blackberry) to 76.1% (cornel), and vitamin P - from 81.9 (sea-buckthorn) to 92.8% (cornel). Stability of titrable acids, except for medlar fruits, varied from 84.2% (blackberry) to 94.0% (sea-buckthorn). The safety of phenolic and pectinaceous compounds by the end of 9 months of storage, has averaged 90.6 and 95.6% respectively in comparison with their initial quantity in fresh fruits. The mineral composition was the stablest. After completion of experiment the safety of mineral substances in fruits of wild plants fluctuated from 94.6 to 98.5%. Distinctions in change of biochemical complexes of berries of blackberry, cornel, medlar and sea-buckthorn at fast freezing (t=-30 °С) and storage (t=-18 °С), apparently, are caused by specific features, content of free and bound water, thickness of cellular walls, durability of a thin skin of fruits, as well as by concentration of the components that inhibit the destructive processes occurring at the cellular and molecular level.


Increased serum levels of interleukin-17 in patients with alopecia areata and non-segmental vitiligo.
Alopecia areata (AA) and vitiligo are both skin diseases of autoimmune origin. AA is characterized by patchy hair loss primarily on the scalp but may involve other areas as well, while vitiligo is caused by the destruction of melanocytes and results in the appearance of white patches on any part of the body. Many facts indicate similar pathogenesis of these diseases. Both dermatoses are associated with frequent coexistence of other autoimmune diseases and share common genetic risk factors. Recent data support the theory of the involvement of IL-17 in the pathogenesis of both AA and vitiligo. To evaluate and compare the serum levels of interleukin (IL)-17 in patients with AA and non-segmental vitiligo (NSV). To assess whether the pattern of serum cytokine concentration can be associated with clinical details and activity of the disease. A cross-sectional study was conducted on 33 patients with AA, 30 patients with NSV, and 30 healthy controls. Serum levels of IL-17 were determined quantitatively by ELISA method. Our analysis identified a systemic inflammatory signature associated with AA and NSV, characterized by elevated levels of IL-17. The levels of IL-17 did not differ significantly between AA patients and NSV patients. Our results show that AA and vitiligo may share common etiopathogenetic pathways, which suggests the potential of developing targeted therapies for both AA and vitiligo treatment. Imbalance of T cell subpopulations and complex systemic cytokine profiles may contribute to the pathogenesis of AA and vitiligo.


Overview of the pathogenesis and treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulins.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired heterogeneous disorder of immune origin affecting the peripheral nerves, causing motor weakness and sensory symptoms and signs. The precise pathophysiology of CIDP remains uncertain although B and T cell mechanisms are believed to be implicated. Intravenous immunoglobulins (IVIg) have been shown in a number of trials to be an effective treatment for CIDP. IVIg is thought to exert its immunomodulatory effects by affecting several components of the immune system including B-cells, T-cells, macrophages and complement. This article provides an overview of the pathogenesis of CIDP and of its treatment with IVIg.


Impact of Left Atrial Appendage Morphology on Recurrence in Embolic Stroke of Undetermined Source and Atrial Cardiopathy.
Background: The left atrial appendage (LAA) is a major source of thrombus and non-chicken wing (CW). LAA morphology is a risk factor for embolic events in atrial fibrillation. However, the association of non-CW morphology with embolic stroke recurrence is unknown in patients with embolic stroke of undetermined source (ESUS) and atrial cardiopathy. Methods: We conducted retrospective analyses using a prospective institutional stroke registry (2013-2017). Patients with ESUS and atrial cardiopathy were enrolled. Atrial cardiopathy was diagnosed if an increased left atrial diameter (>40 mm, men; >38 mm, women), supraventricular tachycardia, or LAA filling defect on computed tomography (CT) were present. Patients admitted >24 h after onset were excluded. LAA morphology was evaluated using CT and categorized into CW vs. non-CW types. The primary outcome was embolic stroke recurrence. Multivariable Cox proportional hazards models were used to examine the independent association between LAA morphology and outcome. Results: Of 157 patients, 81 (51.6%) had CW LAA morphology. The median follow-up was 41.5 (interquartile range 12.3-58.5) months corresponding to 509.8 patient years. In total, 18 participants experienced embolic stroke recurrences (3.80 per 100 patient-years). Non-CW morphology was more associated with embolic stroke recurrence than CW morphology (hazard ratio (HR), 3.17; 95% confidence interval (CI), 1.13-8.91; p = 0.029). After adjusting for CHA2DS2-VASc score and number of potential embolic sources, non-CW morphology showed an independent association with outcome (adjusted HR, 2.90; 95% CI, 1.02-8.23; p = 0.045). Conclusions: The LAA morphology types may help identify high risk of embolic stroke recurrence in ESUS with atrial cardiopathy. LAA morphology in atrial cardiopathy may provide clues for developing therapies tailored to specific mechanisms.


Prevalence and correlates of excessive fatigue among Moroccan school adolescents: A cross-sectional study.
Excessive fatigue in adolescents is a growing concern as it impacts various aspects of their lives. Research on its prevalence and contributing factors in specific populations, especially in developing countries, is scarce. This study examines the prevalence of excessive fatigue among Moroccan adolescents and its association with demographic characteristics, parasomnias, depressive symptoms, and academic performance. In this cross-sectional study, we assessed excessive fatigue among 800 Moroccan adolescents (aged 12-20 years) in Settat province, using a comprehensive questionnaire including Pichot's Fatigue Scale (PFS), Patient Health Questionnaire 9 (PHQ-9), parasomnia questionnaire, and demographic questionnaire. The primary outcome was excessive fatigue, while covariates included demographic factors, physical health, regular exercise, depressive symptoms, and specific parasomnias. Associations were analyzed using cross-tabulation analysis, chi-squared tests, and correlation analysis. Excessive fatigue was prevalent in 8.4% of participants. Female adolescents had significantly higher adjusted odds of experiencing excessive fatigue than male adolescents, with an adjusted odds ratio (AOR) of 3.07 [95% CI (1.48, 6.37), P=0.003]. Excessive fatigue was significantly associated with nightmares, sleep paralysis, and hypnagogic hallucinations. A strong positive linear correlation was observed between fatigue and depressive symptoms (r=0.746, P#x003C;0.001). This study highlights the prevalence of excessive fatigue among Moroccan adolescents, emphasizing the importance of addressing gender-specific issues, sleep habits, and mental health support. Further research is needed to understand the underlying mechanisms and explore the role of lifestyle and socio-cultural contexts.


Effects of heavy metal on rat liver microsomal Ca2(+)-ATPase and Ca2+ sequestering. Relation to SH groups.
In isolated hepatic microsomal vesicles the heavy metals Cd2+, Cu2+, and Zn2+ inhibit Ca2+ uptake and evoke a prompt efflux of Ca2+ from preloaded vesicles in a dose-dependent manner. N-Ethylmaleimide also inhibits Ca2+ uptake and causes Ca2+ release, but it is less effective in these respects than the heavy metals. Measurement of mannose-6-phosphatase activity indicate that the heavy metal-induced Ca2+ efflux is not caused by a general increase in membrane permeability. Heavy metals also inhibit the Ca2(+)-ATPase activity and the formation of the phosphorylated intermediate of the enzyme. In contrast, the sulfhydryl modifying reagent, N-ethylmaleimide inhibits the Ca2(+)-ATPase activity while it has a relatively small effect on Ca2+ release. Thus, the effects of these agents on Ca2+ sequestering and Ca2(+)-ATPase activity are not strictly proportional. The sulfhydryl group reducing agent dithiothreitol protects the microsomes from the effects of heavy metals, while glutathione is less protective. Addition of vanadate to vesicles, at a concentration which completely blocked the activity of the Ca2(+)-ATPase, resulted in a small and slow release of the accumulated Ca2+. Subsequent additions of heavy metals evoked a massive Ca2+ release. Thus, the effects of heavy metals on Ca2+ efflux cannot be due entirely to their inhibition of the Ca2+ pump. The heavy metal-induced Ca2+ efflux is not inhibited either by ruthenium red or tetracaine.


Low Power Laser Therapy: A Strategy to Promote the Osteogenic Differentiation of Deciduous Dental Pulp Stem Cells from Cleft Lip and Palate Patients.
Dental pulp stem cells (DPSCs) can undergo several types of differentiation, including osteogenic differentiation. One osteogenesis-inducing factor that has been previously described is in vitro low-power laser irradiation of cells. Laser irradiation promotes the acceleration of bone matrix mineralization of the cell strain. However, no consensus exists regarding the dose and treatment time. We used DPSC strains from cleft lip and palate patients because new bone tissue engineering strategies have used DPSCs in preclinical and clinical trials for the rehabilitation of alveolar bone clefts. Optimizing bone tissue engineering techniques for cleft and lip palate patients by applying low-power laser therapy (LPLT) to DPSCs obtained from these patients can help improve current strategies to quickly close large alveolar clefts. The aim of this study was to investigate the effects of LPLT at different energy densities in DPSC strains obtained from cleft lip and palate patients during in vitro osteogenic differentiation. Ten DPSC strains were obtained from cleft lip and palate patients and then used in the following study groups: group 1: control, the strains underwent osteogenic differentiation for 21 days; and groups 2, 3, and 4: the strains were irradiated each day with a low-power red laser (660 nm) (5, 10, and 20 J) during 21 days of osteogenic differentiation. Using Bonferroni's test, a statistically significant difference in the mean values was found between the irradiated groups (2, 3, and 4) and the control group (p < 0.001). However, no significant difference in osteogenic potential was found among the irradiated groups. Our findings showed that the osteogenic potential of DPSCs increases with red laser irradiation at 5, 10, and 20 J, and this treatment could be considered a new approach for preconditioning these cells to be used in bone tissue engineering.


Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-analysis of Randomized Trials.
We aimed to compare the effectiveness of single- vs multiple-strain probiotics in a network meta-analysis of randomized trials. We searched MEDLINE, Embase, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through January 1, 2019, for studies of single-strain and multistrain probiotic formulations on the outcomes of preterm, low-birth-weight neonates. We used a frequentist approach for network meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Primary outcomes included all-cause mortality, severe necrotizing enterocolitis (NEC) (Bell stage II or more), and culture-proven sepsis. We analyzed data from 63 trials involving 15,712 preterm infants. Compared with placebo, a combination of 1 or more Lactobacillus species (spp) and 1 or more Bifidobacterium spp was the only intervention with moderate- or high-quality evidence of reduced all-cause mortality (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.39-0.80). Among interventions with moderate- or high-quality evidence for efficacy compared with placebo, combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp, Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced severe NEC (OR, 0.35 [95% CI, 0.20-0.59]; OR, 0.31 [95% CI, 0.13-0.74]; OR, 0.55 [95% CI, 0.34-0.91]; and OR, 0.44 [95% CI, 0.21-0.90], respectively). There was moderate- or high-quality evidence that combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp and Saccharomyces boulardii reduced the number of days to reach full feeding (mean reduction of 3.30 days [95% CI, reduction of 5.91-0.69 days]). There was moderate- or high-quality evidence that, compared with placebo, the single-species product B animalis subsp lactis or L reuteri significantly reduced duration of hospitalization (mean reduction of 13.00 days [95% CI, reduction of 22.71-3.29 days] and mean reduction of 7.89 days [95% CI, reduction of 11.60-4.17 days], respectively). In a systematic review and network meta-analysis of studies to determine the effects of single-strain and multistrain probiotic formulations on outcomes of preterm, low-birth-weight neonates, we found moderate to high evidence for the superiority of combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp vs single- and other multiple-strain probiotic treatments. The combinations of Bacillus spp and Enterococcus spp, and 1 or more Bifidobacterium spp and Streptococcus salivarius subsp thermophilus, might produce the largest reduction in NEC development. Further trials are needed.


Phylogenetic analysis and characterization of lipolytic activity of halophilic archaeal isolates.
Five isolates designated as B45, D83A, A206A, A85 and E49 and found to possess a activity were taxonomically classified on the basis of their phylogenetic, phenotypic and chemotaxonomic characteristics. The isolates were determined to be Gram-negative, catalase and oxidase positive, hydrolyzing Tween 80 and 60 but not starch, need 3.5-4 M NaCl for optimal growth and lack of anaerobic growth with arginine or DMSO. All isolates had the highest lipolytic activity at pH 8.5. Lipase and esterase activities increased with salt concentration up to 3-4.5 M NaCl, and decreased at 5 M NaCl. Esterase and lipase showed their maximal activities at 50-55 degrees C and 60-65 degrees C, respectively. The phylogenetic tree constructed by the neighbor-joining method indicated that the strain B45 and A85 were closely related to the members of genera Halovivax and Natrinema, respectively. The closest relative of the strain A206A and D83A were found to be Haloterrigena saccharevitans. The strain E49 displayed a more distant relationship to known strains.


Spent substrate from mushroom cultivation: exploitation potential toward various applications and value-added products.
Spent mushroom substrate (SMS) is the residual biomass generated after harvesting the fruitbodies of edible/medicinal fungi. Disposal of SMS, the main by-product of the mushroom cultivation process, often leads to serious environmental problems and is financially demanding. Efficient recycling and valorization of SMS are crucial for the sustainable development of the mushroom industry in the frame of the circular economy principles. The physical properties and chemical composition of SMS are a solid fundament for developing several applications, and recent literature shows an increasing research interest in exploiting that inherent potential. This review provides a thorough outlook on SMS exploitation possibilities and discusses critically recent findings related to specific applications in plant and mushroom cultivation, animal husbandry, and recovery of enzymes and bioactive compounds.


Flow Cytometric Analysis of Monocytes and Granulocytes May Be Useful in the Distinction of Myeloid Neoplasms from Reactive Conditions: A Single Institution Experience and Literature Review.
To determine if the immunophenotype of monocytes and granulocytes could help differentiate between reactive conditions and myeloid neoplasms. We analyzed 94 patients including acute myeloid leukemia (n=53), myelodysplastic syndrome (n=19), chronic myelomonocytic leukemia (n=13), and chronic myelogenous leukemia (n=9). Twenty-five cases of reactive condition were included as controls. Myeloid neoplasm cases showed significantly altered expression patterns including overexpression of CD56, altered expression of HLA-DR, underexpression of CD14, CD64, and altered expression of CD33 when compared to controls. There are significant and consistent differences in immunophenotype of monocytes and granulocytes in neoplastic groups versus controls. Immunophenotypic evaluation of monocytes and granulocytes in addition to blasts may be useful in flow cytometric assessment of minimal residual disease in myeloid neoplasms.


Validation of the graded prognostic assessment index for surgically treated patients with brain metastases.
The purpose of this study was to evaluate the performance of the new Graded Prognostic Assessment (GPA) index, which was recently developed from data in the Radiation Therapy Oncology Group (RTOG) database, in patients treated with surgical resection of brain metastases and postoperative whole-brain radiotherapy. The authors analyzed 64 patients and assigned each patient to each of the four indices previously evaluated by the RTOG (recursive partitioning analysis class, Score Index for Radiosurgery, Basic Score for Brain Metastases and GPA). The present data confirm the validity of the scoring systems in surgically treated patients. Each of the four indices splits the dataset into prognostically different groups; in the GPA groups, median survival was 18.9, 9.8, 5.5, and 3.7 months, respectively (p<0.05). In conclusion, these results confirm the validity of the GPA index in a patient population that previously has not been assessed with this new tool.


High-order hydrodynamics via lattice Boltzmann methods.
In this work, closure of the Boltzmann-Bhatnagar-Gross-Krook (Boltzmann-BGK) moment hierarchy is accomplished via projection of the distribution function f onto a space H(N) spanned by N-order Hermite polynomials. While successive order approximations retain an increasing number of leading-order moments of f , the presented procedure produces a hierarchy of (single) N-order partial-differential equations providing exact analytical description of the hydrodynamics rendered by ( N-order) lattice Boltzmann-BGK (LBBGK) simulation. Numerical analysis is performed with LBBGK models and direct simulation Monte Carlo for the case of a sinusoidal shear wave (Kolmogorov flow) in a wide range of Weissenberg number Wi=taunuk(2) (i.e., Knudsen number Kn=lambdak=square root Wi); k is the wave number, [corrected] tau is the relaxation time of the system, and lambda approximately tauc(s) is the mean-free path, where c(s) is the speed of sound. The present results elucidate the applicability of LBBGK simulation under general nonequilibrium conditions.


Antioxidant and antidiabetic activity of blackberry after gastrointestinal digestion and human gut microbiota fermentation.
Blackberry fruit contains high levels of polyphenols particularly anthocyanins which contribute to its biological activities. Bioavailability of polyphenols especially anthocyanins is generally low, it has been proposed that metabolites from polyphenol biotransformation under colonic fermentation are components that exert health benefits. In this study, blackberry was subjected to simulated gastrointestinal digestion and gut microbiota fermentation at different time intervals (0-48 h) to study the changes in bioactive components, its antioxidant and antidiabetic activities. Phenolic compounds, during digestion and fermentation were also analysed. Gut metabolites of blackberry significantly increased the glucose consumption and glycogen content in HepG2 cells. Furthermore, gut metabolites ameliorated high glucose plus palmitic acid-induced ROS overproduction, mitochondrial membrane collapse, and glutathione depletion in HepG2 cells. The mechanism of antidiabetic activity of blackberry was via its potent antioxidant activity. Therefore, our results suggest that blackberry could be recommended as a functional food due to potential antioxidant and antidiabetic activity.


Relationship between individual-cow udder health status in early lactation and dairy cow characteristics in Brittany, France.
Data from a 4-year ecopathological survey involving 47 dairy farms in Brittany (France) were used to determine the individual animal characteristics associated with the udder health profiles of clinical and subclinical mastitis, and the presence of minor or major pathogens in milk during early lactation. Herd effect was taken into account and a within-herd analysis using factorial correspondence analysis and a decomposition of chi-square distance was performed. In primiparous cows, the main association observed was between milk production and intramammary infections with major pathogens. The dirtiness score showed contradictory relationships with udder health profiles. The indoor/outdoor transition period was unfavourable for udder health status; since the frequency rate of subclinical and clinical mastitis increased during this period. In multiparous cows, intramammary infections by minor or major pathogens were closely associated with non-infectious udder diseases, but the main effect was due to parity. Old cows were generally affected by higher somatic cell counts than younger cows regardless of whether the SCC were associated with clinical mastitis or not.


Visual segmentation of complex naturalistic structures in an infant eye-tracking search task.
An infant's everyday visual environment is composed of a complex array of entities, some of which are well integrated into their surroundings. Although infants are already sensitive to some categories in their first year of life, it is not clear which visual information supports their detection of meaningful elements within naturalistic scenes. Here we investigated the impact of image characteristics on 8-month-olds' search performance using a gaze contingent eye-tracking search task. Infants had to detect a target patch on a background image. The stimuli consisted of images taken from three categories: vegetation, non-living natural elements (e.g., stones), and manmade artifacts, for which we also assessed target background differences in lower- and higher-level visual properties. Our results showed that larger target-background differences in the statistical properties scaling invariance and entropy, and also stimulus backgrounds including low pictorial depth, predicted better detection performance. Furthermore, category membership only affected search performance if supported by luminance contrast. Data from an adult comparison group also indicated that infants' search performance relied more on lower-order visual properties than adults. Taken together, these results suggest that infants use a combination of property- and category-related information to parse complex visual stimuli.


Effects of organophosphorus anticholinesterases on nicotinic receptor ion channels at adult mouse muscle endplates.
1. The effects of a range of organophosphorus anticholinesterases on the nicotinic acetylcholine receptor ion channel at the adult mouse muscle endplate were investigated by use of single-channel recording techniques. Diisopropylfluorophosphate (DFP), sarin and soman had no effect on open times at concentrations of up to 100 microM, but ecothiopate (Eco) and O-ethyl S-[2-(diisopropylamino)ethyl]methyl phosphonothiolate (VX) were found to have voltage- and concentration-dependent open channel-blocking actions at concentrations of 1-50 microM. In addition to its channel-blocking action, Eco (50 microM) had a weak agonist effect: it is suggested that this may be attributable to thiocholine produced by hydrolysis of Eco. 2. Rate constants for blockade by Eco and VX were determined according to a sequential model. The greater voltage-dependence of the block by Eco was due to a greater voltage sensitivity of the blocking rate constant compared to VX: the voltage-dependence of the unblocking rate constant was similar for both compounds. 3. In control recordings, the frequency of channel opening declined exponentially with time after formation of the gigaseal. Sarin and soman both increased the rate of this decline, indicating that they accelerated the rate of desensitization of the receptors. Eco and VX reduced the initial frequency of opening, which may have been due to enhancement of a fast phase of desensitization during gigaseal formation, or to blockade of closed channels. 4. It is concluded that the direct actions of organophosphates on nicotinic receptor ion channels are of little importance for their toxicity under normal conditions, since they occur only at much higher concentrations than those which cause inhibition of acetylcholinesterase. Such actions may become apparent, however, when therapies against the anticholinesterase effects of organophosphates increase their lethal dose sufficiently. These direct actions should also be taken into account when the effects of organophosphates on cholinergic transmission are studied.


Using item response theory to investigate the structure of anticipated affect: do self-reports about future affective reactions conform to typical or maximal models?
In the present research, we used item response theory (IRT) to examine whether effective predictions (anticipated affect) conforms to a typical (i.e., what people usually do) or a maximal behavior process (i.e., what people can do). The former, correspond to non-monotonic ideal point IRT models, whereas the latter correspond to monotonic dominance IRT models. A convenience, cross-sectional student sample (N = 1624) was used. Participants were asked to report on anticipated positive and negative affect around a hypothetical event (emotions surrounding the start of a new business). We carried out analysis comparing graded response model (GRM), a dominance IRT model, against generalized graded unfolding model, an unfolding IRT model. We found that the GRM provided a better fit to the data. Findings suggest that the self-report responses to anticipated affect conform to dominance response process (i.e., maximal behavior). The paper also discusses implications for a growing literature on anticipated affect.


Cytotoxic potency of cardiotoxin from Naja sputatrix: development of a new cytolytic assay.
The possible involvement of specific regions/loops of cardiotoxin from Naja sputatrix venom in mediating its cytolytic activity is evaluated using a new cytolytic assay. In this assay, the amount of chloramphenicol acetyltransferase (CAT) that is released upon lysis of the cellular membranes by the cytotoxin has been measured as an index of cytolysis. This newly developed CAT system is more sensitive than the traditional haemolysis method utilizing red blood cells or the lactate dehydrogenase assay for cytolysis. Series of chimaeric toxin molecules have been constructed by swapping the loops between highly hydrophilic neurotoxin and highly hydrophobic cardiotoxin molecules from Naja sputatrix, which are known to exhibit structural similarity (three-finger conformation) but to have different functional properties. Comparison of the cytolytic activities of the recombinant chimaeric toxins demonstrated the possible involvement of all three loops of cardiotoxin in its cytolytic potency. However, the first two loops of the protein appear to make the major contribution to its lytic activity. cDNAs encoding cardiotoxin and the chimaeric toxins, when expressed in transfected cultured Chinese hamster ovary cells, resulted in cell lysis, indicating that these cDNAs can be developed as useful cytolytic agents.


Persistent left fifth aortic arch associated with tetralogy of Fallot.
A case of persistent left fifth aortic arch, forming a congenital "double-lumen" aortic arch, has been diagnosed on angiocardiography during life. It appeared as an unusual vascular structure running inferiorly and parallel to the "real" aortic arch from the innominate artery to the left subclavian artery superior to the pulmonary artery. This anomaly was found in the setting of tetralogy of Fallot, an association never described before, with patent ductus arteriosus (previously reported in most cases). The left aortic arch in this case was not a source of pulmonary circulation, as described in previous cases with pulmonary atresia and ventricular septal defect, but was a systemic-to-systemic connection without functional relevance.


Hypothalamic and suprachiasmatic uptake of serotonin in vitro: twenty-four-hour changes in male and proestrous female rats.
Twenty-four-hour changes in the in vitro serotonin (5-HT) uptake capacity of hypothalamic homogenates and of "Vibratome" slices of the suprachiasmatic nuclear region (SNR) of the hypothalamus were studied in 60-90-day-old Holtzman (albino) rats. Animals acclimated to artificially illuminated (fluorescent, LD 12:12) and temperature controlled (22 +/- 2 C) rooms were killed 6% each of 8 time points. Synaptosomal fractions from homogenates of whole hypothalamus, and slices of the SNR were incubated for 20 min in Krebs-Henseleit buffer with [3H]5-HT. Males showed a single daily peak in SNR uptake at the start of darkness, and a minimum near the onset of light, while a more complex pattern containing 3 peaks and minima occurred in uptake by hypothalamic homogenates. Proestrous females showed a single high amplitude peak SNR uptake during the critical period, just prior to the plasma LH peak determined in the same animals by radioimmunoassay. It is suggested that this short-term and 4-fold increase in SNR uptake of 5-HT may serve to limit free 5-HT and its inhibitory or other effects on the gonadotropin release hormone system and thereby on LH release and ovulation.


Coherent Subcycle Optical Shock from a Superluminal Plasma Wake.
We propose exploiting the superluminal plasma wake for coherent Cherenkov radiation by injecting a relativistic electron beam (REB) into a plasma with a slowly varying density up-ramp. Using three-dimensional particle-in-cell and far-field time-domain radiation simulations, we show that an isolated subcycle pulse is coherently emitted towards the Cherenkov angle by bubble-sheath electrons successively at the rear of the REB-induced superluminal plasma wake. A theoretical model based on a superluminal current dipole has been developed to interpret such coherent radiation, and agrees well with the simulation results. This radiation has ultrashort attosecond-scale duration and high intensity, and exhibits excellent directionality with ultralow angular divergence and stable carrier envelope phase. Its intensity increases with the square of the propagation length and its central frequency can be easily tuned over a wide range, from the far infrared to the ultraviolet.


Meta-analysis of studies examining long-term construction injury rates.
The construction industry is one of the employment sectors with the highest risk of injuries. To evaluate the injury trend in the construction industry from data published from 1987 to 2010. All papers with at least two measurements of injuries within a medium- to long-term period were included. The numbers of fatal and non-fatal injuries were examined in two separate groups: 100,000 workers per year and 200,000 worked hours per year. All injuries significantly decreased between the first and the second measurement, with fatal injuries decreasing by 35% and non-fatal ones by 33% in workers/year and by 22% in worked hours/year. There was high heterogeneity among the sources of data for workers/year index (I(2) = 49% for fatal injuries, 99% for non-fatal injuries) but no heterogeneity for worked hours/year index (I(2) = 0). Meta-regression analysis showed a significant linear relationship between time and risk reduction for fatal injuries (r = 0.63; P < 0.001; a 6% reduction per year); trend reduction for non-fatal injuries was not related to the time taken between the measurements. Fatal injuries have a reduction trend that depends on large interventions, whereas non-fatal injuries are more prone to episodic changes. Furthermore, while the workers/year index allows easier evaluation of the injury rate variation in a single working environment, the worked hours/year index is better at comparing the injury rate variation in different working environments because it reduces the sources of heterogeneity.


Papular purpuric gloves and socks syndrome. Presentation of a clinical case.
Papular-Purpuric Glove-and-Sock Syndrome is a rare, infectious disease, of viral etiology, characterized by the presence of pruritus, edema and symmetrical erythema, very well defined at the wrists and ankles with a gloves-and-socks distribution. Other areas can be affected, with a moderate erythema appearing in cheeks, elbows, knees, armpits, abdomen, groin, external genitalia, internal face of the thighs and the buttocks. Erosions, small ulcers, enanthema and blisters can be observed in the oral cavity and lips, and less frequently in other mucous membranes. Complications are rare, although they can be severe, 50% of the published cases are related with the Parvovirus B19. Due to its oral involvement stomatologists should be aware of this syndrome in order to carry out a correct diagnosis of the disease.


Tyrosine kinase inhibitors. 1. Structure-activity relationships for inhibition of epidermal growth factor receptor tyrosine kinase activity by 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids and 2,2'-dithiobis(1H-indole-3-alkanoic acids).
A series of 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids, and their methyl esters were prepared, the majority by oxidation of 1H-indole-3-alkanoic acids (DMSO/HCl), followed by thiation of the corresponding 2,3-dihydro-2-oxo-1H-indole-3-alkanoic acid esters. The monomeric thiones undergo facile and reversible oxidation to the corresponding 2,2'-dithiobis(1H-indole-3-alkanoic acids). The compounds were evaluated for their abilities to inhibit the tyrosine kinase activity of the epidermal growth factor receptor using a native complex contained in plasma membrane vesicles shed from cultured A431 cells, and to inhibit the growth of Swiss 3T3 mouse fibroblast in culture. Enzyme inhibitory activity is dependent on the length of the side chain, with propanoic acid derivatives showing the highest activity. The acids are generally significantly more potent than the corresponding esters, and the disulfides more active than the corresponding monomers. An ability to undergo the thione-thiol tautomerism necessary for dimerization is essential, with 3,3-disubstituted compounds being inactive. Overall, the data suggest that the disulfide is the more active form, with much of the activity of the monomeric thiones being due to varying degrees of conversion to the disulfide during the assay. In the growth inhibition assay, the methyl esters are more potent than their corresponding carboxylic acids, and the dimers are generally more potent than the monomers. The data show these compounds to be a novel and potent class of inhibitors of epidermal growth factor receptor tyrosine kinase activity.


Quantitative but not qualitative variation in MHC class II alters CD4 interaction and influences T cell repertoire formation.
The influence of the interaction between CD4 and MHC class II molecules on selection of the T cell repertoire was studied in transgenic mice expressing human or human/mouse hybrid MHC class II beta chains. Either wild-type DR beta chains (DR1 beta) or hybrid beta chains comprising the beta1 domain of DR and the beta2, transmembrane, and intracytoplasmic domains of I-E (DRbeta 1Ebeta2) were introduced into and expressed in transgenic mice as a heterodimer with endogenous I-E alpha. Mice expressing low levels of DR1beta:I-E alpha or those expressing low or higher levels of the hybrid DRbeta 1Ebeta2:I-E alpha were studied. Immunization with a suboptimal dose of influenza nucleoprotein peptide exposed a fivefold lower frequency of DR-restricted, peptide-specific, IL-2-secreting T cells in the mice with low-level expression of DRbeta1 Ebeta2:I-E alpha when compared to mice expressing the same molecule at higher levels. The frequency in DRbeta wild-type mice was only twofold lower than that measured in mice with comparable levels of expression of DRbeta 1Ebeta2. These results suggest that positive selection is sensitive to quantitative variation in MHC class II density, unmasked when antigen is limiting, but is relatively insensitive to qualitative variation in the MHC class II: CD4 interaction.


[Comparative Efficacy of the Influence of Fixed Combinations of Antihypertensive Drugs That Block the Renin-Angiotensin-Aldosterone System, With Thiazide Diuretics on the Parameters of Ambulatory Blood Pressure Monitoring].
to compare effects of fixed-dose combinations of antihypertensive drugs that block renin-angiotensin-aldosterone system (RAAS) with hydrochlorothiazide (HCT) on parameters of ambulatory blood pressure monitoring (ABPM). Patients (n=50; 25 women, 25 men aged 40-75 years) with stage II essential hypertension who received no antihypertensive therapy for 12 weeks were randomized to receive once daily fixed-dose combinations of either valsartan/HCT (Val/HCT - group I) or quinapril/HCT (Quin/HCT - groupII) in starting doses of 80/12.5 or 10/12.5 mg, respectively. If target BP (<140 and 90 mm Hg) was not achieved after 2 weeks, doses were increased to 160/12.5 and 20/12.5 mg, respectively. Patients in whom target BP was not achieved after another 2 weeks were excluded from the study. Follow - up after achieving target BP was 12 weeks. Both combinations significantly (p<0.001) reduced office systolic and diastolic BP (SBP and DBP), however, BP decrease in group I was significantly (p<0.01) greater (-42.0+/-2,7 /-22.2+/-1.2 mm Hg) than in group II (-26,4+/-2,1/-6.6+/-0.4 mm Hg). Significant reduction of day- and night-time BP (p<0.001) observed in both groups was also more pronounced (p<0.01) in group I. In both groups we recorded significant (p<0.01) decreases of BP variability and morning BP rise. Variability of DBP at night (-3.3+/-0.2 mm Hg), magnitude and speed of morning DBP surge (-20.9+/-0.3 mm Hg and -3.4+/-0.2 mm Hg/hour, respectively) in group I decreased significantly (p<0.05) greater compared with same parameters in group II (-2.5+/-0.2 mm Hg, -17.7+/-0.3 mm Hg, -2.6+/-0.2 mm Hg/hour, respectively). Fixed-dose combinations of RAAS blockers and HCT provided reliable reduction of BP, BP variability, morning BP rise, and high percentage of achievement of target BP. Val/HCT combination was more effective in terms of reducing SBP, DBP and pulse BP levels at routine measurement, and day- and night-time SBP and DBP, night-time DBP variability, and rate of morning DBP rise.


Ink-jet printing of cu-ag-based highly conductive tracks on a transparent substrate.
We have developed a Cu-Ag-based mixed metal conductive ink from which highly conductive tracks form on a flexible substrate after annealing at low temperature. Addition of small Ag particles significantly improves the particle packing density by filling the interstices formed between the larger Cu particles, which in turn facilitates better conductivity compared to pure Cu metal film. The particle size and volume ratio of the Ag particles added should be carefully controlled to achieve maximum packing density in the bimodal particle system, which is consistent with the theoretical considerations of the Furnas model. In addition, we demonstrate direct writing of complex patterns that exhibit high conductivity upon annealing at sufficiently low temperature (175-210 degrees C) to not damage the transparent plastic substrate such as polyethersulphone (PES).


Signatures of superfluidity for Feshbach-resonant Fermi gases.
We consider atomic Fermi gases where Feshbach resonances can be used to study the whole BCS-Bose-Einstein condensate crossover. We show how a probing field transferring atoms out of the superfluid can be used to detect the onset of the superfluid transition in the high-T(c) and BCS regimes. The number of transferred atoms, as a function of the energy given by the probing field, peaks at the gap energy. The shape of the peak is asymmetric due to the single particle excitation gap. Since the excitation gap also includes a pseudogap contribution, the asymmetry alone is not a signature of superfluidity. The incoherent nature of the noncondensed pairs leads to broadening of the peak. The broadening decays below the critical temperature, causing a drastic increase in the asymmetry. This provides a signature of the transition.


Hyaluronan synthesis by developing cortical neurons in vitro.
Hyaluronan is a linear glycosaminoglycan that forms the backbone of perineuronal nets around neurons in the cerebral cortex. However, it remains controversial whether neurons are capable of independent hyaluronan synthesis. Herein, we examined the expression of hyaluronan and hyaluronan synthases (HASs) throughout cortical neuron development in vitro. Enriched cultures of cortical neurons were established from E16 rats. Neurons were collected at days in vitro (DIV) 0 (4 h), 1, 3, 7, 14, and 21 for qPCR or immunocytochemistry. In the relative absence of glia, neurons exhibited HAS1-3 mRNA at all time-points. By immunocytochemistry, puncta of HAS2-3 protein and hyaluronan were located on neuronal cell bodies, neurites, and lamellipodia/growth cones from as early as 4 h in culture. As neurons matured, hyaluronan was also detected on dendrites, filopodia, and axons, and around synapses. Percentages of hyaluronan-positive neurons increased with culture time to ~93% by DIV21, while only half of neurons at DIV21 expressed the perineuronal net marker Wisteria floribunda agglutinin. These data clearly demonstrate that neurons in vitro can independently synthesise hyaluronan throughout all maturational stages, and that hyaluronan production is not limited to neurons expressing perineuronal nets. The specific structural localisation of hyaluronan suggests potential roles in neuronal development and function.


The effect of crash characteristics on cyclist injuries: An analysis of Virginia automobile-bicycle crash data.
This paper examines bicyclist, automobile driver, vehicle, environmental, and roadway characteristics that influence cyclist injury severity in order to determine which factors should be addressed to mitigate the worst bicyclist injuries. An ordered probit model is used to examine single bicycle-single vehicle crashes from Virginia police crash report data from 2010 to 2014. Five injury severity levels are considered: fatalities, severe injuries, minor or possible injuries, no apparent injuries, and no injury. The results of this study most notably found automobile driver intoxication to increase the probability of a cyclist fatality six fold and double the risk of a severe injury, while bicyclist intoxication increases the probability of a fatality by 36.7% and doubles the probability of severe injury. Additionally, bicycle and automobile speeds, obscured automobile driver vision, specific vehicle body types (SUV, truck, and van), vertical roadway grades and horizontal curves elevate the probability of more severe bicyclist injuries. Model results encourage consideration of methods to reduce the impact of biking and driving while intoxicated such as analysis of bicycling under the influence laws, education of drunk driving impacts on bicyclists, and separation of vehicles and bicycles on the road. Additionally, the results encourage consideration of methods to improve visibility of bicyclists and expectation of their presence on the road.


Simplified sizing of low-density lipoprotein using polyacrylamide gradient gel electrophoresis of plasma.
Low-density lipoprotein (LDL) particles can be separated into subfractions according to size by non-denaturing polyacrylamide gradient gel electrophoresis. Established research methods require specialised equipment and are frequently unsuited to the clinical laboratory. In this study, we utilised a colour flat bed scanner in conjunction with shareware image analysis software to compare LDL particle diameters of isolated LDL with LDL in whole plasma. LDL was isolated by ultracentrifugation and electrophoresed on 3-13% gels (Gradipore; Sydney, Australia) for 2400 Volt-hours in parallel with plasma and molecular size standards. Coomassie Blue-stained gels were scanned in reflexive mode using a colour flat-bed scanner and Adobe Photoshop 3.0 software. Density traces of each lane were obtained using NIH Image software (public domain, USA). LDL particle diameters were determined from calibration curves of the log of molecular diameter of standards against migration distance. There was a good correlation between LDL particle diameters obtained using isolated LDL and whole plasma (r = 0.87, P < 0.001; n = 22). However, the group means (+/- S.D.) (24.7 +/- 0.6 and 24.8 +/- 0.5 nm respectively) were statistically different on the paired t-test (P < 0.05). It is unclear whether this numerically small difference is due to alterations in LDL during the longer preparative procedures for LDL, or to matrix effects during electrophoresis of plasma samples. In conclusion, plasma samples stained with Coomassie Blue and scanned with a colour flat bed scanner can conveniently be used for LDL particle sizing by non-denaturing polyacrylamide gradient gel electrophoresis.


Suppression of lethal ischemic ventricular arrhythmias by the class III agent E4031 in a canine model of previous myocardial infarction.
The antiarrhythmic efficacy of a new and potent class III agent E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl]-4-(4- methylsulfonylaminobenzoyl)piperidine] was evaluated in several canine models of recent myocardial infarction. In anesthetized dogs with baseline inducible ventricular arrhythmias studied 4-10 days after anterior myocardial infarction, 30-300 micrograms/kg i.v. E4031 suppressed induction of ventricular tachyarrhythmias by programmed ventricular stimulation in 7 of 10 animals tested, while significantly prolonging refractoriness in both noninfarcted and infarcted ventricular myocardium. The incidence of lethal ischemic ventricular arrhythmias developing in response to acute posterolateral myocardial ischemia in the presence of previous anterior infarction was reduced from 10 of 10 (100%) in a vehicle pretreatment group to 3 of 10 (30%, p less than 0.01) in an E4031 (300 micrograms/kg intravenously, i.v.) pretreatment group. Neither the sizes of the underlying anterior myocardial infarctions (26.9 +/- 3.7 vs. 33.2 +/- 2.1% of left ventricle) nor the times to development of acute posterolateral myocardial ischemia (43 +/- 11 vs. 40 +/- 8 min) differed significantly between the vehicle and E4031 pretreatment groups, respectively, suggesting that the reduction in the incidence of lethal ischemic arrhythmias in the E4031 pretreatment group was not due to smaller underlying, electrically unstable myocardial substrates nor to a delay in onset of the acute ischemic insult. In conscious dogs with spontaneous ventricular ectopy at 48 h after myocardial infarction and in anesthetized dogs with no baseline inducible arrhythmias at 4-10 days after myocardial infarction, E4031 (30-3,000 micrograms/kg i.v.) produced no facilitation or aggravation of spontaneous or inducible ventricular arrhythmias. These findings suggest that pharmacologic agents such as E4031 that increase ventricular refractoriness (class III electrophysiologic activity) may provide significant protection against development of malignant ischemic ventricular arrhythmias in the setting of previous myocardial infarction.


In Silico Prediction of Organ Level Toxicity: Linking Chemistry to Adverse Effects.
In silico methods to predict toxicity include the use of (Quantitative) Structure-Activity Relationships ((Q)SARs) as well as grouping (category formation) allowing for read-across. A challenging area for in silico modelling is the prediction of chronic toxicity and the No Observed (Adverse) Effect Level (NO(A)EL) in particular. A proposed solution to the prediction of chronic toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL itself. This review has focussed on the use of structural alerts to identify potential liver toxicants. In silico profilers, or groups of structural alerts, have been developed based on mechanisms of action and informed by current knowledge of Adverse Outcome Pathways. These profilers are robust and can be coded computationally to allow for prediction. However, they do not cover all mechanisms or modes of liver toxicity and recommendations for the improvement of these approaches are given.


Risk factors for small airway obstruction among Chinese island residents: a case-control study.
We investigated the prevalence of and risk factors for small airway obstruction (SAO) among Chinese island residents to establish means to prevent and treat SAO. From October 17, 2011 to November 1, 2011, a total of 2,873 residents aged >20 years who lived on the Huangqi Peninsula of Fujian were recruited by random cluster sampling. They were asked to complete a Burden of Obstructive Lung Disease (BOLD) questionnaire and underwent physical examinations and lung function evaluations. SAO was defined as a forced expiratory flow at 50% of vital capacity, Vmax50%, of less than 70% of predicted. Risk factors for SAO were assessed from among demographic and anthropometric variables, blood chemistry results, and questionnaire response items. A total of 216 (7.52%) Chinese island residents were identified as having SAO (95 males; 121 females). Their survey and test results were compared with 432 age and sex-matched healthy controls (192 males; 240 females) for SAO risk factors. Among numerous factors investigated, only diabetes mellitus (p = 0.039), smoking index (SI, p<0.001 for SI>600), second hand smoke (p = 0.002), and lack of regular exercise (p<0.001) were significant risk factors for SAO. The risk factors for SAO among Chinese island residents appeared to be similar to those among people who live in high-density urban environments and impoverished rural areas. Public health policies and medical practices directed toward improving respiratory health for island residents should be comparable to those used for urban and rural dwellers.


Global characterization of differential gene expression profiles in mouse Vγ1+ and Vγ4+ γδ T cells.
Peripheral γδ T cells in mice are classified into two major subpopulations, Vγ1+ and Vγ4+, based on the composition of T cell receptors. However, their intrinsic differences remain unclear. In this study, we analyzed gene expression profiles of the two subsets using Illumina HiSeq 2000 Sequencer. We identified 1995 transcripts related to the activation of Vγ1+ γδ T cells, and 2158 transcripts related to the activation of Vγ4+ γδ T cells. We identified 24 transcripts differentially expressed between the two subsets in resting condition, and 20 after PMA/Ionomycin treatment. We found that both cell types maintained phenotypes producing IFN-γ, TNF-α, TGF-β and IL-10. However, Vγ1+ γδ T cells produced more Th2 type cytokines, such as IL-4 and IL-5, while Vγ4+ γδ T cells preferentially produced IL-17. Our study provides a comprehensive gene expression profile of mouse peripheral Vγ1+ and Vγ4+ γδ T cells that describes the inherent differences between them.


[Cutaneous diphtheria].
Cutaneous diphtheria, frequently seen in tropical areas, is uncommon in developed countries. As seen in the recent epidemics in western countries, where it turned out to be an important factor of dissemination, there is a persisting risk of diphtheria. A perfect knowledge of the clinical manifestations and factors of risk and consequent vaccination is necessary to eradicate diphtheria.


Study of uranium transfer across the blood-brain barrier.
Uranium is a heavy metal which, following accidental exposure, may potentially be deposited in human tissues and target organs, the kidneys and bones. A few published studies have described the distribution of this element after chronic exposure and one of them has demonstrated an accumulation in the brain. In the present study, using inductively coupled plasma mass spectrometry (ICP-MS) for the quantification of uranium, uranium transfer across the blood-brain barrier (BBB) has been assessed using the in situ brain perfusion technique in the rat. For this purpose, a physiological buffered bicarbonate saline at pH 7.4 containing natural uranium at a given concentration was perfused. After checking the integrity of the BBB during the perfusion, the background measurement of uranium in control rats without uranium in the perfusate was determined. The quantity of uranium in the exposed rat hemisphere, which appeared to be significantly higher than that in the control rats, was measured. Finally, the possible transfer of the perfused uranium not only in the vascular space but also in the brain parenchyma is discussed.


Protective effects of astragaloside IV on db/db mice with diabetic retinopathy.
Diabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the potential biological functions of astragaloside IV (AS IV) have long been described in traditional system of medicine, its protective effect on DR remains unclear. This study aims to investigate the function and mechanism of AS IV on type 2 diabetic db/db mice. Db/db mice were treated with AS IV (4.5 mg/kg or 9 mg/kg) or physiological saline by oral gavage for 20 weeks along with db/m mice. In each group, retinal ganglion cell (RGC) function was measured by pattern electroretinogram (ERG) and apoptosis was determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Blood and retina aldose reductase (AR) activity were quantified by chemiluminescence analysis. The expressions of phosporylated-ERK1/2, NF-κB were determined by Western blot analysis. Furthermore, the expression of related downstream proteins were quantified by Label-based Mouse Antibody Array. Administration of AS IV significantly improved the amplitude in pattern ERG and reduced the apoptosis of RGCs.in db/db mice. Furthermore, downregulation of AR activity, ERK1/2 phosphorylation, NF-κB and related cytokine were observed in AS IV treatment group. Our study indicated that AS IV, as an inhibitor of AR, could prevent the activation of ERK1/2 phosporylation and NF-kB and further relieve the RGCs disfunction in db/db mice with DR. It has provided a basis for investigating the clinical efficacy of AR inhibitors in preventing DR.


Natural Holobiome Engineering by Using Native Extreme Microbiome to Counteract the Climate Change Effects.
In the current scenario of climate change, the future of agriculture is uncertain. Climate change and climate-related disasters have a direct impact on biotic and abiotic factors that govern agroecosystems compromising the global food security. In the last decade, the advances in high throughput sequencing techniques have significantly improved our understanding about the composition, function and dynamics of plant microbiome. However, despite the microbiome have been proposed as a new platform for the next green revolution, our knowledge about the mechanisms that govern microbe-microbe and microbe-plant interactions are incipient. Currently, the adaptation of plants to environmental changes not only suggests that the plants can adapt or migrate, but also can interact with their surrounding microbial communities to alleviate different stresses by natural microbiome selection of specialized strains, phenomenon recently called "Cry for Help". From this way, plants have been co-evolved with their microbiota adapting to local environmental conditions to ensuring the survival of the entire holobiome to improve plant fitness. Thus, the strong selective pressure of native extreme microbiomes could represent a remarkable microbial niche of plant stress-amelioration to counteract the negative effect of climate change in food crops. Currently, the microbiome engineering has recently emerged as an alternative to modify and promote positive interactions between microorganisms and plants to improve plant fitness. In the present review, we discuss the possible use of extreme microbiome to alleviate different stresses in crop plants under the current scenario of climate change.


Rapid volume expansion in the Torpedo electric organ associated with its postsynaptic potential.
By electrically stimulating Torpedo electric organs enclosed in a sealed plastic chamber, it was demonstrated that the production of a postsynaptic potential is accompanied by a rapid increase in the volume of the organ. This increase started almost simultaneously with the onset of the postsynaptic potential and reached its maximum at about the end of the potential. The volume returned slowly to its resting level. Repetitive stimulation produced a summation of volume changes. The maximum change evoked by a single electric shock was roughly 10(-6) times the electrocyte volume. The thermal expansion of the organ associated with the production of a postsynaptic potential accounts for roughly 25% or less of this volume increase. The possibility is pointed out that a cation-exchange process involving Ca2+ on anionic sites in the electrocyte protoplasm may be at the base of the volume changes.


Evaluation of the root and canal morphology of mandibular permanent anterior teeth in an Iranian population by cone-beam computed tomography.
To evaluate differences in the root and canal configurations of mandibular permanent anterior incisors and canines in an Iranian population by means of Cone Beam CT (CBCT) images. Four hundred CBCT images of mandibular permanent incisors and canines that met the inclusion criteria were evaluated. Vertucci's classification was used to evaluate the number of roots, number of root canals, root lengths, root curvatures and canal types. Totally 632 central incisors, 614 lateral incisors and 608 canines were evaluated. The average length of the mandibular central, lateral incisors and canines was 21.3±0.10, 21.9± 0.13 and 25.1± 0.11 mm, respectively. All of the mandibular central and lateral incisors had one root, but the incidence of single-rooted mandibular canines and two-rooted mandibular canines was 96.3% and 4.7%, respectively. The majority of mandibular central, lateral incisors and canines had one canal (72.7%, 70.6% and 71.8%, respectively). Five types of Vertucci canal configurations were seen in the evaluated teeth. Type 1 Vertucci configuration was the most prevalent configuration (72.3%, 70.6% and 71.8% for the central, lateral incisors and canines, respectively)), and type 5 Vertucci canal configuration was the least prevalent type seen (3.3%, 3.2% and 2.3% for the central, lateral incisors and canines, respectively). The most frequent root curvatures in these teeth were distally and buccally. No significant difference was seen between male and female patients regarding any of the parameters evaluated in this study (p>0.05). More attention should be given to the detection of additional canals and the recognition of canal curvature in Iranian patients.


Cancer-associated fibroblasts induce high mobility group box 1 and contribute to resistance to doxorubicin in breast cancer cells.
Cancer-associated fibroblasts and high mobility group box 1 (HMGB1) protein have been suggested to mediate cancer progression and chemotherapy resistance. The role of such fibroblasts in HMGB1 production in breast cancer is unclear. This study aimed to investigate the effects of cancer-associated fibroblasts on HMGB1 expression in breast cancer cells and its role in chemotherapeutic response. Breast cancer-associated fibroblasts (BCFs) and non-tumor-associated fibroblasts (NTFs) were isolated from human breast cancers or adjacent normal tissues and established as primary cultures in vitro. After confirmation of the activated status of these fibroblasts, conditioned-media (CM) were collected and applied to MDA-MB-231 human triple negative breast cancer cells. The levels of intracellular and extracellular HMGB1 were measured by real-time PCR and/or Western blot. The response of BCF-CM-pre-treated cancer cells to doxorubicin (Dox) was compared with those pre-treated with NTF-CM or control cultures. The effect of an HMGB1 neutralizing antibody on Dox resistance induced by extracellular HMGB1 from non-viable Dox-treated cancer cells or recombinant HMGB1 was also investigated. Immunocytochemical analysis revealed that BCFs and NTFs were alpha-smooth muscle actin (ASMA) positive and cytokeratin 19 (CK19) negative cells: a phenotype consistent with that of activated fibroblasts. We confirmed that the CM from BCFs (but not NTFs), could significantly induce breast cancer cell migration. Intracellular HMGB1 expression was induced in BCF-CM-treated breast cancer cells and also in Dox-treated cells. Extracellular HMGB1 was strongly expressed in the CM after Dox-induced MDA-MB-231 cell death and was higher in cells pre-treated with BCF-CM than NTF-CM. Pre-treatment of breast cancer cells with BCF-CM induced a degree of resistance to Dox in accordance with the increased level of secreted HMGB1. Recombinant HMGB1 was shown to increase Dox resistance and this was associated with evidence of autophagy. Anti-HMGB1 neutralizing antibody significantly reduced the effect of extracellular HMGB1 released from dying cancer cells or of recombinant HMGB1 on Dox resistance. These findings highlight the potential of stromal fibroblasts to contribute to chemoresistance in breast cancer cells in part through fibroblast-induced HMGB1 production.


Two phase 2 trials of the novel Akt inhibitor perifosine in patients with advanced renal cell carcinoma after progression on vascular endothelial growth factor-targeted therapy.
The clinical activity of allosteric inhibitors of mammalian target of rapamycin (mTOR) inhibitors in renal cell carcinoma (RCC) may be limited by upstream activation of phosphatidylinositol 3 (PI3)-kinase/Akt resulting from mTOR1 inhibition. On the basis of this rationale, 2 independent phase 2 trials (Perifosine 228 and 231) were conducted to assess the efficacy and safety of the novel Akt inhibitor perifosine in patients with advanced RCC who had failed on previous vascular endothelial growth factor (VEGF)-targeted therapy. In the Perifosine 228 trial, 24 patients with advanced RCC received oral perifosine (100 mg daily). Perifosine 231 enrolled 2 groups that received daily oral perifosine (100 mg daily): Group A comprised 32 patients who had received no prior mTOR inhibitor, and Group B comprised 18 patients who had received 1 prior mTOR inhibitor. In the Perifosine 228 trial, 1 patient achieved a partial response (objective response rate, 4%; 95% confidence interval, 0.7%-20%), and 11 patients (46%) had stable disease as their best response. The median progression-free survival was 14.2 weeks (95% confidence interval, 7.7-21.6 weeks). In the Perifosine 231 trial, 5 patients achieved a partial response (objective response rate, 10%; 95% confidence interval, 4.5%-22.2%) and 16 patients (32%) had stable disease as their best response. The median progression-free survival was 14 weeks (95% confidence interval, 12.9, 20.7 weeks). Overall, perifosine was well tolerated, and there were very few grade 3 and 4 events. The most common toxicities included nausea, diarrhea, musculoskeletal pain, and fatigue. Although perifosine demonstrated activity in patients with advanced RCC after failure on VEGF-targeted therapy, its activity was not superior to currently available second-line agents. Nonetheless, perifosine may be worthy of further study in RCC in combination with other currently available therapies.


Paxillin and embryonic PolyAdenylation Binding Protein (ePABP) engage to regulate androgen-dependent Xenopus laevis oocyte maturation - A model of kinase-dependent regulation of protein expression.
Steroid-triggered Xenopus laevis oocyte maturation is an elegant physiologic model of nongenomic steroid signaling, as it proceeds completely independent of transcription. We previously demonstrated that androgens are the main physiologic stimulator of oocyte maturation in Xenopus oocytes, and that the adaptor protein paxillin plays a crucial role in mediating this process through a positive feedback loop in which paxillin first enhances Mos protein translation, ensued by Erk2 activation and Erk-dependent phosphorylation of paxillin on serine residues. Phosphoserine-paxillin then further augments Mos protein translation and downstream Erk2 activation, resulting in meiotic progression. We hypothesized that paxillin enhances Mos translation by interacting with embryonic PolyAdenylation Binding Protein (ePABP) on polyadenylated Mos mRNA. Knockdown of ePABP phenocopied paxillin knockdown, with reduced Mos protein expression, Erk2 and Cdk1 activation, as well as oocyte maturation. In both Xenopus oocytes and mammalian cells (HEK-293), paxillin and ePABP constitutively interacted. Testosterone (Xenopus) or EGF (HEK-293) augmented ePABP-paxillin binding, as well as ePABP binding to Mos mRNA (Xenopus), in an Erk-dependent fashion. Thus, ePABP and paxillin work together in an Erk-dependent fashion to enhance Mos protein translation and promote oocyte maturation.


Reaction Optimization of Strontium Perchlorate Catalyzed Novel Protocol for Stereoselective Synthesis of Dihydropyrimidinones.
Hydrated strontium perchlorate [Sr(ClO4)2.3H2O] acts as a very strong oxidizing and dehydrating agent. Until now, it could not be reported as a catalyst in dehydration mechanism-based organic synthetic reactions. Therefore, it is important to find whether it could be an effective catalyst for one-pot multicomponent reactions (MCRs). The main objective of the present work is the development of a novel process for the synthesis of 1,4-dihydropyrimidinones through the one-pot multicomponent strategy using hydrated Sr(ClO4)2 as a catalyst. Furthermore, it includes process optimization, stereoselectivity, and spectroscopic characterization of the synthesized compounds. Conventional and microwave-supported synthesis of 1,4-dihydropyrimidinones using 20 mol % of hydrated Sr(ClO4)2 catalyst via the one-pot solvent-free reaction was discovered as a new catalytic MCR methodology. The box-Behnken design approach and advanced analytical techniques were used for process optimization and reaction analysis. The results confirmed that hydrated Sr(ClO4)2; works as an efficient catalyst for one-pot multicomponent organic synthesis under both conventional and microwave heating. It is an effective catalyst for laboratory synthesis of 1,4-dihydropyrimidinones stereoselectively with moderate to excellent yield without any undesirable effect. Microwave heating provided the desired product within 1-4 minutes. Moreover, this method provides easy isolation of the pure products simply by recrystallization, and without the use of a chromatographic purification method. The simplicity and neutrality of reaction conditions, easy post-reaction workup, higher satisfactory to excellent yield, effectiveness, the diversity of substrates, etc. render the hydrated Sr(ClO4)2 catalyst-based protocol for the stereoselective synthesis of 1,4-dihydropyrimidinones as a highly efficient method. Furthermore, it has been found to be safe un-der laboratory reaction conditions and no undesirable issues have been faced during the process.


Primary liver cancer in a referral hospital in Hawaii.
This is a retrospective review of 43 patients who had primary liver cancer diagnosed during 1974-1983. Patients' ages ranged from 27 to 84 years (median 52.5). Nine of 39 patients with hepatoma were females, while two of the four patients with cholangiocarcinoma were women. Hepatitis surface antigen was positive in 90% tested, and 62% had cirrhosis. Also, 60-65% were heavy users of alcohol and cigarettes. Alpha-fetoprotein was elevated in one of four white patients, and in six of eight patients of other races (75%). Tissue diagnosis was obtained by peritoneoscopy in 16, by percutaneous biopsy in 7, by laparotomy in 9, and at autopsy in 11. Only one of 11 patients who were explored has his lesion resected. About half of the cases diagnosed antemortem died 1 month or less after diagnosis. The median survival of hepatoma patients who had no specific treatment or systemic chemotherapy was 2 months. Two patients who received chemotherapy in conjunction with occlusion of the hepatic artery lived 16 to 19 months.


Quantitative Assessment of Fundus Tessellated Density and Associated Factors in Fundus Images Using Artificial Intelligence.
This study aimed to quantitative assess the fundus tessellated density (FTD) and associated factors on the basis of fundus photographs using artificial intelligence. A detailed examination of 3468 individuals was performed. The proposed method for FTD measurements consists of image preprocessing, sample labeling, deep learning segmentation model, and FTD calculation. Fundus tessellation was extracted as region of interest and then the FTD could be obtained by calculating the average exposed choroid area of per unit area of fundus. Besides, univariate and multivariate linear regression analysis have been conducted for the statistical analysis. The mean FTD was 0.14 ± 0.08 (median, 0.13; range, 0-0.39). In multivariate analysis, FTD was significantly (P < 0.001) associated with thinner subfoveal choroidal thickness, longer axial length, larger parapapillary atrophy, older age, male sex and lower body mass index. Correlation analysis suggested that the FTD increased by 33.1% (r = 0.33, P < .001) for each decade of life. Besides, correlation analysis indicated the negative correlation between FTD and spherical equivalent (SE) in the myopia participants (r = -0.25, P < 0.001), and no correlations between FTD and SE in the hypermetropia and emmetropic participants. It is feasible and efficient to extract FTD information from fundus images by artificial intelligence-based imaging processing. FTD can be widely used in population screening as a new quantitative biomarker for the thickness of the subfoveal choroid. The association between FTD with pathological myopia and lower visual acuity warrants further investigation. Artificial intelligence can extract valuable clinical biomarkers from fundus images and assist in population screening.


Human substantia nigra neurons encode decision outcome and are modulated by categorization uncertainty in an auditory categorization task.
The ability to categorize stimuli - predator or prey, friend or foe - is an essential feature of the decision-making process. Underlying that ability is the development of an internally generated category boundary to generate decision outcomes. While classic temporal difference reinforcement models assume midbrain dopaminergic neurons underlie the prediction error required to learn boundary location, these neurons also demonstrate a robust response to nonreward incentive stimuli. More recent models suggest that this may reflect a motivational aspect to performing a task which should be accounted for when modeling dopaminergic neuronal behavior. To clarify the role of substantia nigra dopamine neurons in uncertain perceptual decision making, we investigated their behavior using single neuron extracellular recordings in patients with Parkinson's disease undergoing deep brain stimulation. Subjects underwent a simple auditory categorical decision-making task in which they had to classify a tone as either low- or high-pitched relative to an explicit threshold tone and received feedback but no reward. We demonstrate that the activity of human SN dopaminergic neurons is predictive of perceptual categorical decision outcome and is modulated by uncertainty. Neuronal activity was highest during difficult (uncertain) decisions that resulted in correct responses and lowest during easy decisions that resulted in incorrect responses. This pattern of results is more consistent with a "motivational" role with regards to perceptual categorization and suggests that dopamine neurons are most active when critical information - as represented by uncertainty - is available for learning decision boundaries.


[Studies on the anticancer effect of howiinol A, a new compound isolated from Goniothalamus howii].
The effect of howiinol A (GHM-10) on the growth of several cancer and normal cells were studied, using the methods of cell growth curve determination, MTT test and soft-agar colony formation assay. The results showed that GHM-10 exhibited potent inhibitory effect on cancer cells with an IC50 of 2 micrograms.ml-1 approximately. Normal cells, especially bone marrow progenitor cells, were shown to be less sensitive to GHM-10. A drug-resistant cell line, KB/VCR200, was found to be as sensitive as its parental KB cells. GHM-10 did not induce HL-60 cell differentiation. In murine transplantable tumors, GHM-10 was found to have significant therapeutic effect on mice bearing solid tumor hepatoma H22, Lewis lung carcinoma and S180 ascites.


Proptosis and increase of intraocular pressure in voluntary lid fissure widening.
The eyeball proptoses about 0.5 mM and increases in intraocular pressure (IOP) about 2 mmHg with voluntary widening of the lid fissure. The findings probably result from the retraction of the upper lid into the orbit, thus increasing the volume of orbit contents and forcing the eyeball forward. Decrease in IOP with repeated tonometry may result, in part, from decay of the increased pressure induced by lid fissure widening.


[Strategies of treatment of acute obturative colonic ileus].
Results of surgical treatment of 326 patients with an acute obturation colonic ileus (AOCI) were analyzed. Tumor was localized in left half of colon and retrosygmoid part in 76.8% of observations. There were admitted to the hospital 49.1% of patients with AOCI in subcompensation and decompensation stages. Radical operation was done in 65.4% and palliative one--in 34.6% of patients. Decompression of upper and lower parts of the gut, using oxygenated solutions, was done in complex of preoperative preparation and during operation performance. The method of colonic intraoperative decompression was depicted. In 26.3% of patients for AOCI postoperative complications occurred. Mortality have constituted 11.7%: after operation for AOCI in compensation stage--2.4%, while in subcompensation and decompensation--21.3%.


Matrix Metalloproteinase 1 Causes Vasoconstriction and Enhances Vessel Reactivity to Angiotensin II via Protease-Activated Receptor 1.
Matrix metalloproteinase 1 (MMP-1) is an activator of protease-activated receptor 1 (PAR-1), which is known to mediate the release of endothelin 1 (ET-1) in endothelial cells and activate the RhoA kinase (ROCK) pathway. Recently, we reported increased serum and vascular MMP-1 in women with preeclampsia and hypothesized that the action of MMP-1 on PAR-1 might have vasoconstrictive effects. Resistance-sized omental arteries obtained from normal pregnant women were mounted on a myograph system and perfused with MMP-1 in a dose range of 0.025 to 25 ng/mL or with angiotensin II (Ang II) in a dose range of 0.001 to 10 µmol/L in the presence of intraluminal MMP-1 (2.5 ng/mL) perfusion. Angiotensin II dose response was also performed with omental arteries from women with preeclampsia. Matrix metalloproteinase 1 caused dose-dependent vasoconstriction in endothelium-intact, but not in endothelium-denuded, vessels from normal pregnant women, which was blocked by inhibitors of PAR-1 and ET-1 type A receptor blocker. Intraluminal perfusion with a constant amount of MMP-1 enhanced vessel reactivity to Ang II, which was blocked by inhibitors of PAR-1, ROCK, and ET-1. Enhanced vascular reactivity to Ang II was observed in endothelium-intact, but not in endothelium-denuded, arteries of women with preeclampsia. Inhibitors of PAR-1, ROCK, and ET-1 blocked enhanced vascular reactivity to Ang II in endothelium-intact preeclamptic arteries. These data demonstrate that MMP-1 has potent vasoconstrictor effects and the ability to enhance vascular reactivity to vasoconstrictor hormones, which are mediated by an endothelial PAR-1, ROCK, and ET-1 pathway. Increased circulating levels of MMP-1 and its increased expression in systemic vessels of women with preeclampsia may contribute to the development of maternal hypertension.


Longitudinal measurement invariance of the Behavioral Health Measure in a clinical sample.
The practice of routine outcome monitoring (ROM) has grown in popularity and become a fixture in feedback-supported clinical practice and research. However, if the interpretation of an ROM measure changes over time, treatment outcome scores may be inaccurate and produce erroneous or misguided interpretations of client progress and therapist efficacy. The current study examined whether factorial invariance held when using the Behavioral Health Measure (BHM-20) longitudinally in a clinical sample (n = 12,467). Using multidimensional item response theory-based models for the investigation of the BHM-20 factor structure, at a single time point and then longitudinally. Based on the original factor structure of the BHM-20 a unidimensional model, a three-factor orthogonal model, and a three-factor correlated model were fit to the data, indicating poor model fit with the proposed three-factor or unidimensional models. Next, using exploratory factor analysis and subsequent multidimensional item response theory procedures, a new 4-factor (General Distress, Life Functioning, Anxiety, and Alcohol/Drug Use) model was proposed with improved model-fit statistics. Finally, when testing the longitudinal invariance of the BHM-17 over 10 sessions of treatment, it was found to be fully consistent. The current study proposes the use of a 17-item, 4-factor model for a new understanding of the BHM-17. Implications for use in ROM and limitations are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).