Increased Incidence of TdT-negative Pre-B Acute Lymphoblastic Leukemia Associated With Poor Prognostic Features Among Mexican Children in Central Mexico.

Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease ( P =0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL ( P =0.001) and KMT2A gene rearrangement ( P =0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics ( P <0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity.

Gender balance in the workforce and abortion attitudes: A cross-national time-series analysis.

This article explores the relationship between gender balance in the workforce and attitudes towards abortion worldwide. Studies on macro-level conditions related to abortion attitudes overlook the role of gender balance in the workforce-specifically the degree of female representation in a country's workforce. There are strong reasons why this factor could shape abortion attitudes. We argue that such a gender balance creates necessary conditions to break with traditional, anti-abortion ideology and facilitates dissemination and public acceptance of pro-choice views. We test this argument with two different datasets - the Integrated Values Survey and three waves of the International Social Survey Programme-along with two outcomes: general tolerance towards abortion and tolerance towards abortion for pregnant women of low income. Using three-level random intercept models and multiple controls for individual and country-level conditions, the results support our hypothesis: In countries with higher gender balance in the workforce, individuals display higher tolerance towards abortion.

Societal religiosity and the gender gap in political interest, 1990-2014.

This manuscript examines the structural causes of the gender gap in political interest. In many countries, men are more interested in politics than women. Yet, in others, men and women prove equally interested. We explain this cross-national variation by focusing on the effects of societal religiosity. Since religion sustains the traditional gender order, contexts where societal religiosity is low undermine the taken-for-grantedness of this order, subjecting it to debate. Men then become especially interested in politics to try to reassert their traditional gender dominance, or to compensate for their increasingly uncertain social status. A secular environment thus increases political interest more among men than among women, expanding this gender gap. Using the World and European Values Survey, we estimate three-level regression models and test our religiosity-based approach in 96 countries. The results are consistent with our hypothesis.

Peptides from Mucuna pruriens L., with protection and antioxidant in vitro effect on HeLa cell line.

BACKGROUND: Mucuna pruriens L. is a legume sown in the Mexican southeast with an important protein content. Studies have shown the potential use of by-products derived from Mucuna as a functional food because of the hypoglycemic and antihypertensive activities. Thus, this study aims to assess the antioxidant and protective effect of the peptide fractions derived from M. pruriens L., in vitro on the HeLa cell line. An enzymatic hydrolysis with pepsin-pancreatin was performed on the total protein concentrate, from which five peptide fractions were obtained. RESULTS: All protein derivatives from M. pruriens L., except F5-10 kDa, decreased the hydrogen peroxide production by more than 50%. The highest antioxidant activity was exhibited by F1-3 kDa, which lowered the intracellular reactive oxygen species by 207 ± 4.20%. No significant differences were found in the protective effects of the protein hydrolysate, F5-10 kDa, F3-5 kDa and F1-3 kDa relative to the N-acetylcysteine control group. CONCLUSION: This elucidated the potential action mechanisms of M. pruriens L. protein derivatives for future investigations and their role in the prevention and treatment of oxidative stress. © 2019 Society of Chemical Industry.

Protein hydrolysates and ultrafiltered < 1 KDa fractions from Phaseolus lunatus, Phaseolus vulgaris and Mucuna pruriens exhibit antihyperglycemic activity, intestinal glucose absorption and α-glucosidase inhibition with no acute toxicity in rodents.

BACKGROUND: Protein hydrolysates from food plants, such as legumes, have emerged as a new alternative to treat hyperglycemia, an important risk factor contributing to the development of type 2 diabetes mellitus (T2DM) and its complications. The aim of this work was to assess the antihyperglycemic activity and inhibition of α-glucosidase, and intestinal glucose absorption, and acute toxicity of total hydrolysates and < 1 kDa fractions from Phaseolus lunatus L., Phaseolus vulgaris L., and Mucuna pruriens (L.) DC., obtained by hydrolysis with Alcalase®-Flavourzyme® or pepsine-pancreatin enzymatic systems. RESULTS: In vivo results showed that three of six total hydrolysates and four of six < 1 kDa fractions suppressed starch-induced postprandial hyperglycemia (ED50 range between 1.4 and 93 mg kg-1 ). In vitro, total hydrolysates and fractions, particularly from M. pruriens, inhibited carbohydrate intestinal absorption (from 19.2 to 40%), and α-glucosidase activity (IC50 from 0.86 to 75 mg mL-1 ). Finally, none of the hydrolysates and fractions tested did not show any signs of toxicity (LD50 > 5000 mg kg-1 ). CONCLUSION: These results suggest that hydrolysates and < 1 kDa fractions from P. lunatus, P. vulgaris and M. pruriens are suitable candidates to treat or prevent T2DM. © 2018 Society of Chemical Industry.

In vitro renin-angiotensin system inhibition and in vivo antihypertensive activity of peptide fractions from lima bean (Phaseolus lunatus L.).

BACKGROUND: The renin-angiotensin system is key in the physiopathology of arterial hypertension because it converts angiotensin I, via angiotensin I-converting enzyme (ACE), into angiotensin II. In vitro analyses were done of the ACE-inhibitory and renin-inhibitory activities of peptide fractions isolated by enzymatic hydrolysis of lima bean (Phaseolus lunatus) protein. Antihypertensive activity was confirmed in vivo using a rat model. RESULTS: Lima bean protein was hydrolyzed with one of two sequential enzymatic systems (pepsin-pancreatin or Alcalase®-Flavourzyme®). Ultrafiltration of the hydrolysates produced fractions of different molecular weights. The >3 kDa fraction of the pepsin-pancreatin hydrolysate had the highest ACE-inhibitory activity (60.15%, IC50: 172.62 µg mL-1 ), while the >3 KDa fraction of the Alcalase®-Flavourzyme® hydrolysate had the highest in vitro renin-inhibitory activity. A weak correlation (r = 0.44) was found between ACE-inhibitory and renin-inhibitory activities. When tested in vivo, the latter fraction lowered systolic blood pressure by 64% and diastolic blood pressure by 51%. CONCLUSION: Peptide fractions from lima bean Phaseolus lunatus protein hydrolysates exhibit both in vitro and in vivo antihypertensive activity. Bioactive peptides from lima bean have potential applications as ingredients in functional foods. © 2017 Society of Chemical Industry.

Manganese-Mediated C-H Alkylation of Unbiased Arenes Using Alkylboronic Acids.

The alkylation of arenes is an essential synthetic step of interest not only from the academic point of view but also in the bulk chemical industry. Despite its limitations, the Friedel-Crafts reaction is still the method of choice for most of the arene alkylation processes. Thus, the development of new strategies to synthesize alkyl arenes is a highly desirable goal, and herein, we present an alternative method to those conventional reactions. Particularly, a simple protocol for the direct C-H alkylation of unbiased arenes with alkylboronic acids in the presence of Mn(OAc)3 ⋅2H2 O is reported. Primary or secondary unactivated alkylboronic acids served as alkylating agents for the direct functionalization of representative polyaromatic hydrocarbons (PAHs) or benzene. The results are consistent with a free-radical mechanism.

Collective religiosity and the gender gap in attitudes towards economic redistribution in 86 countries, 1990-2008.

What is the relationship between gender and the demand for redistribution? Because, on average, women face more economic deprivation than men, in many countries women favor redistribution more than men. However, this is not the case in a number of other countries, where women do not support redistribution more than men. To explain this cross-national paradox, we stress the role of collective religiosity. In many religions, theological principles both militate against public policies designed to redistribute income, and also promote traditionally gendered patterns of work and family involvement. Hence, we hypothesize that, in those countries where religion remains influential either through closer church-state ties or an intensely religious population, men and women should differ less in their attitudes towards redistribution. Drawing upon the World Values Survey, we estimate three-level regression models that test our religiosity-based approach and two alternative explanations in 86 countries and 175 country-years. The results are consistent with our hypothesis. Moreover, in further support of our theoretical approach, societal religiosity undermines pro-redistribution preferences more among women than men. Our findings suggest that collective religiosity matters more to the gender gap in redistributive attitudes than traditional political and labor force factors.

Influence of the HER2 Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients: a meta-analysis.

BACKGROUND: The HER2 655 A>G genetic variant has recently been associated with trastuzumab-induced cardiotoxicity in HER2 breast cancer patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the cardiac toxicity of trastuzumab in breast cancer patients. METHODS: Our study population was composed of 78 HER2 breast cancer patients receiving trastuzumab. The HER2 655 A>G (rs1136201) genetic variant was genotyped using TaqMan allelic discrimination technology. Patients were classified on the basis of the occurrence of cardiotoxic events or the absence of cardiotoxic events during 1 year after the first infusion. RESULTS: The HER2 655 A>G polymorphism was significantly associated with cardiotoxicity: AG versus AA [P=0.012, odds ratio (OR)=5.12, 95% confidence interval (CI) 1.43-18.36], AG+GG versus AA (P=0.01, OR=5.72, 95% CI 1.50-21.76), AG versus AA+GG (P=0.005, OR=7.17, 95% CI 1.82-28.29). A meta-analysis combining these data with the results from previous studies confirmed this association. CONCLUSION: Our results support the role of the HER2 655 A>G polymorphism as a genetic marker of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.

Does Abortion Liberalisation Accelerate Fertility Decline? A Worldwide Time-Series Analysis.

Since WWII, the two most important global trends in family planning have been fertility decline and abortion liberalisation. But are they related? Specifically: Does abortion liberalisation affect changes in fertility rates? The demographic literature has yet to answer this important question and instead offers two opposing predictions. Some studies argue that liberalisation of this medical procedure reduces fertility rates. By contrast, others note that such legal reforms may merely have an average, negligible effect on fertility levels. We adjudicate between the two approaches by conducting, in our view, the most comprehensive global, quantitative analysis of the relationship between those legal reforms and changing fertility rates. The analysis relies on two-way fixed models and three different indicators of abortion policy liberalism created by independent research teams to estimate the relationship between abortion liberalisation and total fertility changes. The data cover 185 independent states between 1970 and 2019. Fertility rates are significantly related to average public education levels and alternative contraceptive use. Using multiple model specifications, however, abortion reforms do not have a robust association with the outcome. Replication materials for this article can be found at https://figshare.com/s/5336a4422f47c8c39228 .

UNVEILING THE SIGNIFICANCE OF DYNAMIC ARTERIAL ELASTANCE: AN INSIGHTFUL APPROACH TO ASSESSING ARTERIAL LOAD IN AN ENDOTOXIN SHOCK MODEL.

ABSTRACT: Background: The aim of this study was to investigate the relationship between dynamic arterial elastance (EaDyn) and the pulsatile and steady components of arterial load in an endotoxin shock model using a two-element Windkessel model and to describe the behavior of EaDyn in this model. Methods : Ten female Yorkshire pigs were administered lipopolysaccharide intravenously to induce endotoxin shock, while three female pigs served as the control group. Measurements of EaDyn (ratio between pulse pressure variation and stroke volume variation), effective arterial elastance, arterial compliance (Cart), and systemic vascular resistance were taken every 30 min in the endotoxin group until shock was induced. In the control group, these variables were measured every 30 min for 3 h. Subsequently, a fluid load was administered to both groups, and measurements were repeated every 30 min. After 1 hour of shock induction, the endotoxin group was divided into two subgroups: one receiving norepinephrine (END-NE) and the other not receiving it (END-F). Results: EaDyn showed an association with Cart, while pulse pressure variation was connected to both pulsatile and steady components, and stroke volume variation was solely associated with steady components. In addition, EaDyn exhibited higher values in the END groups than in the control group when shock was achieved. Furthermore, after the administration of norepinephrine, EaDyn displayed higher values in END-F than in END-NE. Conclusions: The EaDyn variable helps identify changes in the pulsatile component of arterial load, providing valuable guidance for management strategies aimed at improving cardiac performance.

Pension Policy Literacy and Retirement Expectations: A Cross-Country Survey Experiment.

OBJECTIVES: This study reports the findings of the first cross-national survey experiment on the effects of information on the expected retirement age. Given the drawbacks of unrealistic retirement expectations, the study examines the impacts of nonpartisan information about future demographic aging and forecasted pension benefit levels. METHODS: An online survey experiment was conducted in the United States, Germany, and Spain in 2018 using an internet access panel. We assigned respondents to 2 random treatments: one citing the change in the projected share of the population older than 65 years (demographic treatment) and another citing the projected change in pension replacement rates (benefits treatment), both for 2015-2040. Treatment effects on the expected retirement age are reported. RESULTS: The benefits treatment has a strong influence on retirement expectations. In the United States, respondents informed of the expected decline in pension replacement rates expect to retire 2 years later than respondents not informed of the decline. In Spain, this treatment leads to an approximately 9-month postponement of expected retirement, while no significant effect is found in Germany. In addition, the demographic treatment does not affect retirement expectations in the countries studied. Respondents in all countries informed of future population aging do not show different expected retirement ages than respondents not given this information. DISCUSSION: People's retirement expectations are sensitive to information on future changes in pension generosity but not to information on population aging. The results suggest information campaigns focused on declining pension replacement rates may help extend working lives.

Effects of Foam Rolling vs. Manual Therapy in Patients with Tension-Type Headache: A Randomized Pilot Study.

BACKGROUND: This study compares the effect of foam rolling (FR) vs. manual therapy (MT) on pain, pressure pain threshold (PPT), headache disability (HDI) and impact of headache (HIT-6) in patients with tension-type headache (TTH). METHODS: A total of 38 participants with TTH were randomly assigned to an FR group (FRG, n = 13), an MT group (MTG, n = 13) or a control group (CG, n = 12). FRG received FR treatment; MTG received MT techniques; CG received a placebo treatment. The treatment lasted one month. Outcome measures were assessed at baseline, post-intervention and follow-up. RESULTS: Both FRG and MTG showed significant improvements in all variables after the treatment, but the intervention effect was maintained only for functional disability (p = 0.002 and p = 0.005, respectively), overall disability (p = 0.007; p = 0.030) and HIT-6 (p = 0.002; p = 0.001) at follow-up. After treatment, FRG and MTG presented a significantly higher PPT in right (p = 0.044; p = 0.009) and left suboccipital (p = 0.004; p = 0.021). MTG showed a significantly lower HIT-6 than CG (p = 0.008). No differences between FRG and MTG were found in any variable. CONCLUSIONS: Both FR and MT are effective treatments for the improvement of clinical symptoms in TTH. Further studies are needed to confirm our findings in a larger population.

Effect of Enzymatic Digestion of Protein Derivatives Obtained from Mucuna pruriens L. on Production of Proinflammatory Mediators by BALB/c Mouse Macrophages.

Inflammation is considered to be a major risk factor for the pathogenesis of chronic non-communicable diseases. Macrophages are important immune cells, which regulate inflammation and host defense by secretion of proinflammatory mediators. Obtaining biopeptides by enzymatic hydrolysis adds value to proteins of vegetative origin, such as Mucuna pruriens L. The present study evaluated the effect of enzymatic digestion of protein derivatives obtained from M. pruriens L. on the production of proinflammatory mediators by BALB/c mouse macrophages. Five different molecular weight peptide fractions were obtained (F > 10, 5-10, 3-5, 1-3, and < 1 kDa, respectively). At 300 µg/mL, F5-10 kDa inhibited 50.26 and 61.00% NO and H2O2 production, respectively. Moreover, F5-10 kDa reduced the IL-6 and TNFα levels to 60.25 and 69.54%, respectively. After enzymatic digestive simulation, F5-10 kDa decreased the inflammatory mediators.

[Cardiac cephalgia: an underdiagnosed condition? ]. / Cefalea cardíaca: 'una entidad infradiagnosticada?

Cardiac cephalgia, or headache occurring as manifestation of myocardial ischemia, has only recently been recognized as a distinct entity. In patients with known ischemic cardiopathy, its diagnosis depends on the presence of severe headache that is accompanied by nausea, worsened by physical exercise, and only ceases with nitrate administration. We report on two patients who met diagnostic criteria for this entity. In both, headache was the only symptom of coronary ischemia, and delayed its diagnosis. Headache occurred both at rest and during exertion, and resolved only after the administration of nitrates. Cardiac cephalgia should be suspected in patients with a history of ischemic cardiopathy who present with de novo headache, even when thoracic pain is absent, especially if the headache improves with nitrates. Differential diagnosis with migraine is crucial to avoid the administration of vasoconstrictors.

Beyond strong and weak: rethinking postdictatorship civil societies.

What is the impact of dictatorships on postdictatorial civil societies? Bottom-up theories suggest that totalitarian dictatorships destroy civil society while authoritarian ones allow for its development. Top-down theories of civil society suggest that totalitarianism can create civil societies while authoritarianism is unlikely to. This article argues that both these perspectives suffer from a one-dimensional understanding of civil society that conflates strength and autonomy. Accordingly we distinguish these two dimensions and argue that totalitarian dictatorships tend to create organizationally strong but heteronomous civil societies, while authoritarian ones tend to create relatively autonomous but organizationally weak civil societies. We then test this conceptualization by closely examining the historical connection between dictatorship and civil society development in Italy (a posttotalitarian case) and Spain (a postauthoritarian one). Our article concludes by reflecting on the implications of our argument for democratic theory, civil society theory, and theories of regime variation.

Chemical composition by HPLC-ESI-QTOF-MS/MS: Estrogenic and antioxidant effects of Mangifera indica L. cv. "Kent" leave extracts on ovariectomized rats / Composición química por HPLC-ESI-QTOF-MS/MS: efectos estrogénicos y antioxidantes de extractos de Mangifera indica L. cv. "Kent" en ratas ovariectomizadas

The chemical composition of Mangifera indica L. cv. "Kent" leaves was determined by HPLC-ESI-QTOF-MS/MS. Polyphenolic compounds characterized as benzophenone derivatives were the main components found in extracts (1, maclurin 3-C-(2-O-galloyl)-D- glucoside isomer; 2, maclurin 3-C---D-glucoside; 3, iriflophenone 3-C---D-glucoside; 5, maclurin 3-C-(2,3-di-O-galloyl)---D-glucoside; 6, iriflophenone 3-C-(2-O-galloyl)---D-glucoside; 7, methyl-iriflophenone 3-C-(2,6-di-O-galloyl)---D-glucoside) and xanthones (4, mangiferin and 8, 6-O-galloyl-mangiferin). The estrogenic and antioxidant effects of aqueous extracts from Mangifera indica L. cv. "Kent" leaves on ovariectomized rats were determined by uterotrophic assay and malondialdehyde (MDA) levels in erythrocytes, bone, liver, and stomach. We conclude that the polyphenolic compounds from extracts act as exogenous antioxidant agents against oxidative damage in ovariectomized rats.

La composición química de las hojas de Mangifera indica L. cv. "Kent" se determinó por HPLC-ESI-QTOF-MS/MS. Compuestos polifenólicos caracterizados como derivados de benzofenona fueron los componentes principales encontrados en los extractos (1, isómero de la maclurina 3-C-(2-O-galoyil)-D-glucósido; 2, maclurina 3-C-ß-D-glucósido; 3, iriflofenona 3-C-ß-D-glucósido; 5, maclurina 3-C-(2,3-di-O-galloíl)-ß-D-glucósido; 6, iriflofenona 3-C-(2-O-galloil)-ß-D-glucósido; 7, metil-iriflofenona 3-C-(2,6-di-O- galloyl)-ß-D-glucósido) y xantonas (4, mangiferina y 8, 6-O-galoyil-mangiferina). Los efectos estrogénicos y antioxidantes de los extractos acuosos de hojas de Mangifera indica L. cv. "Kent" en ratas ovariectomizadas se determinaron mediante ensayo uterotrófico y la medición de los niveles de malondialdehído (MDA) en eritrocitos, huesos, hígado y estómago. Concluimos que los compuestos polifenólicos de los extractos actúan como agentes antioxidantes exógenos contra el daño oxidativo en ratas ovariectomizadas.

Base- and metal-free C-H direct arylations of naphthalene and other unbiased arenes with diaryliodonium salts.

A novel metal-free direct arylation of unbiased arenes with diaryliodonium triflates in a process where the use of solvents and additives is not required has been established.

Zidovudine induces S-phase arrest and cell cycle gene expression changes in human cells.

Antiretroviral therapy for the human immunodeficiency virus-1 (HIV-1) typically includes two nucleoside reverse transcriptase inhibitors (NRTIs). 3'-Azido-3'-deoxythymidine (AZT, Zidovudine) plus 2'-deoxy-3'-thiacytidine (3TC, Lamivudine) is a combination that is used frequently. The NRTIs are mutagenic nucleoside analogs that become incorporated into DNA and terminate replication. We therefore hypothesized that exposure to this class of drug may alter cell cycle parameters. We used flow cytometry to examine the cell cycle in human epithelioid carcinoma (HeLa) cells exposed to AZT and 3TC alone, as well as a series of AZT/3TC dose combinations: (A) 125.0 microM AZT/12.5 microM 3TC; (B) 250.0 microM AZT/25.0 microM 3TC; and (C) 500 microM AZT/50 microM 3TC. At 24 h, at all doses, there was a good cell viability (>/=68%), and incorporation of AZT into nuclear DNA. Using flow cytometry, a dose-related increase in the percentage of cells in S phase, from 9.5% with no drug, to 36.0% with dose C, was observed in cells exposed for 24 h (P = 0.001, ANOVA). A concomitant decrease in the percentage of cells in G(1) phase, from 82.6% with no drug to 58.5% with dose C, was observed in cells exposed for 24 h (P = 0.017, ANOVA). A similar S phase arrest was seen in cells exposed to 125, 250 and 500 microM AZT alone, but there was no S phase alteration with 50 microM 3TC alone, suggesting that AZT is responsible for the accumulation of cells in S phase. To elucidate the accumulation of cells in S phase and explore the cell cycle gene expression changes induced by AZT and 3TC, we used c-DNA microarray, Cell Cycle Super Array and real-time PCR. There was a strong upregulation of the DNA damage-inducible transcript 3 (DDIT3 or GADD153) in NRTI-exposed cells. In addition, AZT induced an upregulation of cyclin D1 accompanied by a downregulation of the cyclin D1-associated inhibitors P18 and P57, and the G(1)-S check point gene P21, the net effect of which would be to foster a cell progression into S phase. Cyclin A2 was down-regulated in cells exposed to AZT, suggesting a block in S-G(2)-M progression that would also be consistent with the accumulation of cells in S phase. Overall, the study demonstrates that AZT, but not 3TC, causes an arrest of cells in S phase with a consistent alteration in the expression of several cell cycle genes.