A new LC-MS/MS method for simultaneous and quantitative detection of bisphenol-a and steroids in target tissues: A power tool to characterize the interference of bisphenol-a exposure on steroid levels

Bisphenol A (BPA), an endocrine disruptor, may affect in situ steroidogenesis and alter steroids levels. The present work proposes a liquid chromatography tandem mass spectrometry method to simultaneously quantify BPA, 17β-Estradiol and testosterone in two target tissues: testis and visceral fat mass. Analytes were isolated and lipophilic impurities removed by two serial steps: liquid-liquid and solid phase extraction. All compounds were separated in a single gradient run by Kinetex F5 column and detected via multiple reaction monitoring using a triple quadrupole with a TurboIon electrospray source in both negative and positive modes. The method is selective and very sensitive. In the investigated concentration range, the linearity of the detector response is verified in both tissues. The use of specific SPE cartridges for affinity chromatography purification allows obtaining high percentages of process efficiency (68.0-83.3% for testicular tissue; 63.7-70.7% for visceral fat mass). Good repeatability and reproducibility was observed. The validated method can be efficiently applied for direct biological monitoring in testis and visceral fat mass from mice exposed to BPA. The quantification of compounds in a single assay could be achieved without a loss of sensitivity

Characterization of estrogenic activity and site‐specific accumulation of bisphenol‐a in epididymal fat pad: Interfering effects on the endocannabinoid system and temporal progression of germ cells

The objective of this work has been to characterize the estrogenic activity of bisphenol‐A (BPA) and the adverse effects on the endocannabinoid system (ECS) in modulating germ cell progression. Male offspring exposed to BPA during the foetal‐perinatal period at doses below the no‐observed‐adverse‐effect‐level were used to investigate the exposure effects in adulthood. Results showed that BPA accumulates specifically in epididymal fat rather than in abdominal fat and targets testicular expression of 3β‐hydroxysteroid dehydrogenase and cytochrome P450 aromatase, thus promoting sustained increase of estrogens and a decrease of testosterone. The exposure to BPA affects the expression levels of some ECS components, namely type‐1 (CB1) and type‐2 cannabinoid (CB2) receptor and monoacylglycerol‐lipase (MAGL). Furthermore, it affects the temporal progression of germ cells reported to be responsive to ECS and promotes epithelial germ cell exfoliation. In particular, it increases the germ cell content (i.e., spermatogonia while reducing spermatocytes and spermatids), accelerates progression of spermatocytes and spermatids, promotes epithelial detachment of round and condensed spermatids and interferes with expression of cell–cell junction genes (i.e., zonula occcludens protein‐1, vimentin and β‐catenin). Altogether, our study provides evidence that early exposure to BPA produces in adulthood sustained and site‐specific BPA accumulation in epididymal fat, becoming a risk factor for the reproductive endocrine pathways associated to ECS

Overexpression of melanocortin 2 receptor accessory protein 2 (MRAP2) in adult paraventricular MC4R neurons regulates energy intake and expenditure

The Medical Research Council UK (MRC/Academy of Medical Sciences Clinician Scientist Fellowship Grant G0802796 (to LFC) and NIH grants R01 DK105571, DK097566 and DK107293 (to SD)

Evolutionary models for the interaction of the higher education labor force and higher education market

The higher education market portends to be a huge market in the future that traditional systems of delivery of services will be insufficient. This paper proposes a model that links two (2) global markets: the higher education market and the labor market, as dramatic changes are taking place in the 21st century. A modeling and simulation strategy has been employed in this paper predicting the impact of higher education market to the labor market. Results indicated that with the rapid expansion of the higher education market, the size of the higher education labor force will inevitably expand. The labor market tolerates a maximum expansion capacity for HE graduates beyond which the excess HE graduates will bifurcate into two (2) channels of productive sector, namely: (a) the creation of new economies; or (b) the integration of HE graduates into the skilled labor force. This dynamics necessarily yields a highly fragmented labor force con iguration. In essence, the evolution of the labor market is a replica of Darwin’s Biological Theory of Evolution where only the ittest will survive, i.e. evolution through mutation and adaptation whose equivalent concepts in this setting are “innovation” and “adaptation” respectively. It is well-established in Evolutionary Biology that “mutation” is the shortest-route to evolution and so we posit that “innovation” is the shortest route to the labor market evolutionary ladder. Therefore, a good university must be able to produce graduates who are innovative and adaptive at the same time to survive in a competitive labor market

Ecto-nucleoside triphosphate diphosphohydrolase 3 in the ventral and lateral hypothalamic area of female rats: morphological characterization and functional implications

<p>Abstract</p> <p>Background</p> <p>Based on its distribution in the brain, ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) may play a role in the hypothalamic regulation of homeostatic systems, including feeding, sleep-wake behavior and reproduction. To further characterize the morphological attributes of NTPDase3-immunoreactive (IR) hypothalamic structures in the rat brain, here we investigated: 1.) The cellular and subcellular localization of NTPDase3; 2.) The effects of 17β-estradiol on the expression level of hypothalamic NTPDase3; and 3.) The effects of NTPDase inhibition in hypothalamic synaptosomal preparations.</p> <p>Methods</p> <p>Combined light- and electron microscopic analyses were carried out to characterize the cellular and subcellular localization of NTPDase3-immunoreactivity. The effects of estrogen on hypothalamic NTPDase3 expression was studied by western blot technique. Finally, the effects of NTPDase inhibition on mitochondrial respiration were investigated using a Clark-type oxygen electrode.</p> <p>Results</p> <p>Combined light- and electron microscopic analysis of immunostained hypothalamic slices revealed that NTPDase3-IR is linked to ribosomes and mitochondria, is predominantly present in excitatory axon terminals and in distinct segments of the perikaryal plasma membrane. Immunohistochemical labeling of NTPDase3 and glutamic acid decarboxylase (GAD) indicated that γ-amino-butyric-acid- (GABA) ergic hypothalamic neurons do not express NTPDase3, further suggesting that in the hypothalamus, NTPDase3 is predominantly present in excitatory neurons. We also investigated whether estrogen influences the expression level of NTPDase3 in the ventrobasal and lateral hypothalamus. A single subcutaneous injection of estrogen differentially increased NTPDase3 expression in the medial and lateral parts of the hypothalamus, indicating that this enzyme likely plays region-specific roles in estrogen-dependent hypothalamic regulatory mechanisms. Determination of mitochondrial respiration rates with and without the inhibition of NTPDases confirmed the presence of NTPDases, including NTPDase3 in neuronal mitochondria and showed that blockade of mitochondrial NTPDase functions decreases state 3 mitochondrial respiration rate and total mitochondrial respiratory capacity.</p> <p>Conclusion</p> <p>Altogether, these results suggest the possibility that NTPDases, among them NTPDase3, may play an estrogen-dependent modulatory role in the regulation of intracellular availability of ATP needed for excitatory neuronal functions including neurotransmission.</p

Assessing the impact of principal’s instructional leadership, school level, and effectiveness in educational institutions

This study aimed to investigate the relationship between instructional leadership and school effectiveness in educational institutions in Toledo City Division, Philippines. A mixed-methods approach was utilized, including a survey questionnaire and focus group discussions. The survey was administered to 13 school principals, while the focus group discussions involved 14 teachers and school administrators. The quantitative results showed that instructional leadership had a significant positive effect on school effectiveness, while school level did not have a significant effect. The qualitative findings highlighted the challenges faced by school principals in implementing effective instructional leadership practices, including resistance to change and limited resources. The importance of collaboration and communication between school principals, teachers, and the community in promoting effective instructional leadership practices was also emphasized. The comparative analysis of the quantitative and qualitative results revealed that while the survey results showed a significant positive relationship between instructional leadership and school effectiveness, the focus group discussions provided valuable insights into the challenges and strategies for effective implementation of instructional leadership practices. Overall, this study suggests that instructional leadership plays a critical role in enhancing school effectiveness in educational institutions in Toledo City Division, Philippines. The findings highlight the need for collaboration and communication between school leaders, teachers, and the community to ensure the success of instructional leadership practices. These findings have implications for educational policy and practice, emphasizing the importance of investing in instructional leadership development and support to improve school effectiveness

The bisphenol a induced oxidative stress in non-alcoholic fatty liver disease male patients: A clinical strategy to antagonize the progression of the disease

Introduction: Bisphenol A (BPA) exposure has been correlated to non-alcoholic fatty liver disease (NAFLD) development and progression. We investigated, in a clinical model, the effects of the administration of 303 mg of silybin phospholipids complex, 10 μg of vitamin D, and 15 mg of vitamin E (RealSIL, 100D, IBI-Lorenzini, Aprilia, Italy) in male NAFLD patients exposed to BPA on metabolic, hormonal, and oxidative stress-related parameters. Methods: We enrolled 32 male patients with histologic diagnosis of NAFLD and treated them with Realsil 100D twice a day for six months. We performed at baseline clinical, biochemical, and food consumption assessments as well as the evaluation of physical exercise, thiobarbituric acid reactive substances (TBARS), plasmatic and urinary BPA and estrogen levels. The results obtained were compared with those of healthy control subjects and, in the NAFLD group, between baseline and the end of treatment. Results: A direct proportionality between TBARS levels and BPA exposure was shown (p &lt; 0.0001). The therapy determined a reduction of TBARS levels (p = 0.011), an improvement of alanine aminotransferase, aspartate aminotransferase, insulinemia, homeostatic model assessment insulin resistance, C reactive protein, tumor necrosis factor alpha (p &lt; 0.05), an increase of conjugated BPA urine amount, and a reduction of its free form (p &lt; 0.0001; p = 0.0002). Moreover, the therapy caused an increase of plasmatic levels of the native form of estrogens (p = 0.03). Conclusions: We highlighted the potential role of BPA in estrogen oxidation and oxidative stress in NAFLD patients. The use of Realsil 100D could contribute to fast BPA detoxification and to improve cellular antioxidant power, defending the integrity of biological estrogen-dependent pathways

Reading comprehension skills using SQ3R method

The research assessed the four (4) reading comprehension levels among the third year Bachelor of Elementary Education students in terms of the literal, inferential, critical and evaluative skills using SQ3R method. The study utilized the pre-testpost-test design under pre-experimental research design to determine the levels of reading comprehension skills of BEEd students before and after using SQ3R method. In additional, T-test was used to assess the significant difference of students’ reading performance of the two assessments. Furthermore, the simple percentage was used to get the reading comprehension skill levels of the students and the K to 12 standard academic performance to interpret the results. Findings revealed that in the first assessment, the level of reading comprehension of the students was under the beginner level. After they were exposed to SQ3R method in the second assessment, their level move to Approaching Proficiency. The study concluded that using the SQ3R method in teaching reading results to honing reading comprehension skills and may lead readers to proficiency

Enhanced dynamic functional connectivity (whole-brain chronnectome) in chess experts

Multidisciplinary approaches have demonstrated that the brain is potentially modulated by the long-term acquisition and practice of specific skills. Chess playing can be considered a paradigm for shaping brain function, with complex interactions among brain networks possibly enhancing cognitive processing. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) can be useful to explore the effect of chess playing on whole-brain fluidity/dynamism (the chronnectome). Dynamic connectivity parameters of 18 professional chess players and 20 beginner chess players were evaluated applying spatial independent component analysis (sICA), sliding-time window correlation, and meta-state approaches to rs-fMRI data. Four indexes of meta-state dynamic fluidity were studied: i) the number of distinct meta-states a subject pass through, ii) the number of switches from one meta-state to another, iii) the span of the realized meta-states (the largest distance between two meta-states that subjects occupied), and iv) the total distance travelled in the state space. Professional chess players exhibited an increased dynamic fluidity, expressed as a higher number of occupied meta-states (meta-state numbers, 75.8 ± 7.9 vs 68.8 ± 12.0, p = 0.043 FDR-corrected) and changes from one meta-state to another (meta-state changes, 77.1 ± 7.3 vs 71.2 ± 11.0, p = 0.043 FDR-corrected) than beginner chess players. Furthermore, professional chess players exhibited an increased dynamic range, with increased traveling between successive meta-states (meta-state total distance, 131.7 ± 17.8 vs 108.7 ± 19.7, p = 0.0004 FDR-corrected). Chess playing may induce changes in brain activity through the modulation of the chronnectome. Future studies are warranted to evaluate if these potential effects lead to enhanced cognitive processing and if "gaming" might be used as a treatment in clinical practice