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32 mins ago


We further assessed the functions of non-essential CaRSC subunits, showing that the novel subunit Nri1 and the bromodomain subunit Rsc4 play roles in filamentation and stress responses; and also interacted at the genetic level to regulate cell viability. Consistent with these roles, Rsc4 is required for full virulence of C. albicans in the murine model of systemic infection. Taken together, our data builds the first comprehensive study of the composition and roles of RSC in C. albicans, showing both conserved and distinct features compared to model fungal systems. The study illuminates how C. albicans uses RSC-dependent transcriptional regulation to respond to environmental signals and drive survival fitness and virulence in mammals.25-Hydroxyvitamin D [25(OH)D] has been reported to be associated with several chronic liver diseases. The relationship between 25(OH)D and autoimmune hepatitis (AIH) pathogenesis is incompletely understood. We investigated the association of serum total and free 25(OH)D levels with necroinflammatory activity and cytokine levels in 66 patients with AIH diagnosed in our hospital. The median age at AIH diagnosis was 57 years, and the malefemale ratio was 759. The median serum total 25(OH)D level in therapy-naïve patients with AIH was 14.2 ng/mL (interquartile range [IQR], 11.4-17.9 ng/mL). Of the 66 patients with AIH, 36 had serum total 25(OH)D levels of less then 15 ng/mL and were considered to have vitamin D deficiency, and 30 had serum total 25(OH)D levels of ≥ 15 ng/mL. Patients with acute-onset AIH had significantly lower serum total 25(OH)D levels than those with chronic-onset AIH. In particular, serum total 25(OH)D levels were significantly lower in patients with severe forms of AIH. Furthermore, the serum total 25(OH)D level was positively correlated with the serum albumin level and prothrombin time and negatively correlated with the serum total bilirubin level and necroinflammatory activity in AIH. Multivariate logistic regression analysis showed that the serum total 25(OH)D level was an independent factor for severe necroinflammatory activity. Interestingly, AIH patients with serum total 25(OH)D levels of less then 15 ng/mL had higher levels of inflammatory cytokines such as interferon-γ and interleukin-33. Free 25(OH)D levels were correlated with total 25(OH)D levels, and the percentage of free 25(OH)D was significantly associated with necroinflammatory activity. In conclusion, 25(OH)D deficiency may play an important role in predicting AIH severity via inflammatory cytokine production.We showed the results of the first long-term analysis (1987-2019) of pesticide (herbicides, fungicides and insecticides) impact in the Rolling Pampa, one of the main agricultural areas of Argentina. Using a clear and meaningful tool, based not only on acute toxicity but also on scaling up the results to total sown area, we identified time trends for both pesticide impact and the ecoefficiency of modal pesticide profiles. By the end of the time series, soybean showed a pesticide impact four times greater than maize crop in the studied area. However, the time trend in the subperiod (2012-2019) showed a sustainable pattern of pesticide use in soybean crop, with an improvement in its ecoefficiency. Oppositely, maize showed a relatively constant ecoefficiency value during most of the time series, suggesting a possible path towards an unsustainable cropping system. Findings from this study suggest that some efforts have to be made to improve the pest management decisions towards a more efficient pesticide profiles in maize crop and to keep improving the ecotoxicity pesticide profile in soybean crops because of its large sown area in the studied area.
Cervical Cancer is the leading cause of cancer-related deaths among Ethiopian women. Despite many interventions were conducted, there is low uptake of cervical cancer screening services. https://www.selleckchem.com/products/gsk484-hcl.html Also, limited evidence was available on the women's intention and its predictors towards cervical cancer screening. Therefore, this study was aimed at determining the intention and predicators of behavioral intention toward cervical cancer screening.

A cross-sectional study was conducted in the Gomma district, Jimma, Ethiopia from August 1-30, 2019. The total sample sizes were 422 and a systematic random sampling technique was employed to select the samples. Data were collected through interviews using a structured questionnaire guide. Data were entered in epidata, and exported and analyzed using SPSS version 20.0 software. Descriptive, correlation, and multicollinearity analysis were done. Also, simple and multiple linear regression analysis were performed to identify the predictors for behavioral intention. The p-value&Radiotherapy plays a major role in the curative treatment of head and neck cancer, either as a single modality therapy, or in combination with surgery or chemotherapy, or both. Despite advances to limit radiation-induced side-effects, the major salivary glands are often affected. This frequently leads to hyposalivation which causes an increased risk for xerostomia, dental caries, mucositis, and malnutrition culminating in a significant impact on patients' quality of life. Previous research demonstrated that loss of salivary function is associated with a decrease in polarity regulators and an increase in nuclear Yap localization in a putative stem and progenitor cell (SPC) population. Yap activation has been shown to be essential for regeneration in intestinal injury models; however, the highest levels of nuclear Yap are observed in irradiated salivary SPCs that do not regenerate the gland. Thus, elucidating the inputs that regulate nuclear Yap localization and determining the role that Yap plays within the entire tissue following radiation damage and during regeneration is critical. In this study, we demonstrate that radiation treatment increases nuclear Yap localization in acinar cells and Yap-regulated genes in parotid salivary tissues. Conversely, administration of insulin-like growth factor 1 (IGF1), known to restore salivary function in mouse models, reduces nuclear Yap localization and Yap transcriptional targets to levels similar to untreated tissues. Activation of Rho-associated protein kinase (ROCK) using calpeptin results in increased Yap-regulated genes in primary acinar cells while inhibition of ROCK activity (Y-27632) leads to decreased Yap transcriptional targets. These results suggest that Yap activity is dependent on ROCK activity and provides new mechanistic insights into the regulation of radiation-induced hyposalivation.

43 mins ago


A synthetic strategy to fused bicyclic piperidines-building blocks for medicinal chemistry-is developed. The key step was an intramolecular [2 + 2]-photocyclization. The photochemical step was performed on a gram scale. Crystallographic analysis of the obtained compounds revealed that they occupy a novel chemical space and can be considered as elongated analogues of 3-substituted piperidines.The recent "US-China trade war" has aroused concern over trade-related environmental impacts. This study built a multiregional computable general equilibrium model to simulate environmental impacts of the "US-China trade war" under different scenarios of tariff and nontariff barriers and the battlefield spreading ranges. The present study found that although the trade war will cause a global economic downturn, which will seemingly reduce environmental pressure globally, global carbon emissions are expected to increase rather than decline. On the one hand, the CO2 emission increase caused by land-use changes in Brazil and Argentina will far exceed the emission reduction because of decreased global production. On the other hand, some countries/economies especially those developing countries such as Vietnam, Russia, and India will face emission increases driven by scale effects. Countries such as Korea, the UK, and France will enjoy a reduction in emissions driven by structural effects. China and the US will face a reduction in production and CO2 emissions, but their CO2 emission intensities will rise. The results remind us that as global production and supply chains are formed, it is important to closely monitor trade-related environmental impacts. Efforts should be made to balance the interests of trade and the environment.Isolating isomorphic compounds of tetravalent actinides (i.e., ThIV, UIV, NpIV, and PuIV) improve our understanding of the bonding behavior across the series, in addition to their relationship with tetravalent transition metals (Zr and Hf) and lanthanides (Ce). Similarities between these tetravalent metals are particularly illuminated in their hydrolysis and condensation behavior in aqueous systems, leading to polynuclear clusters typified by the hexamer [MIV6O4(OH)4]12+ building block. Prior studies have shown the predominance and coexistence of smaller species for ThIV (monomers, dimers, and hexamers) and larger species for UIV, NpIV, and PuIV (including 38-mers and 70-mers). We show here that aqueous uranium(IV) sulfate also displays behavior similar to that of ThIV (and ZrIV) in its isolated solid-phase and solution speciation. Two single-crystal X-ray structures are described a dihydroxide-bridged dimer (U 2 ) formulated as U2(OH)2(SO4)3(H2O)4 and a monomer-linked hexamer framework (U-U 6 ) as (U(H2O)3.5)2U6O4(OH)4(SO4)10(H2O)9. These structures are similar to those previously described for ThIV. Moreover, cocrystallization of monomer and dimer and of dimer and monomer-hexamer phases for both ThIV (prior) and UIV (current) indicates the coexistence of these species in solution. https://www.selleckchem.com/products/pfi-2.html Because it was not possible to effectively study the sulfate-rich solutions via X-ray scattering from which U 2 and U-U 6 crystallized, we provide a parallel solution speciation study in low sulfate conditions, as a function of the pH. Raman spectroscopy, UV-vis spectroscopy, and small-angle X-ray scattering of these show decreasing sulfate binding, increased hydrolysis, increased species size, and increased complexity, with increasing pH. This study describes a bridge across the first half the actinide series, highlighting UIV similarities to ThIV, in addition to the previously known similarities to the transuranic elements.A new mechanism of allostery in proteins, based on charge rather than structure, is reported. We demonstrate that dynamic redistribution of charge within a protein can control its function and affect its interaction with a binding partner. In particular, the association of an antibody with its target protein antigen is studied. Dynamic charge shifting within the antibody during its interaction with the antigen is enabled by its binding to a metallic surface that serves as a source for electrons. The kinetics of antibody-antigen association are enhanced when charge redistribution is allowed, even though charge injection happens at a position far from the antigen binding site. This observation points to charge-reorganization allostery, which should be operative in addition or parallel to other mechanisms of allostery, and may explain some current observations on protein interactions.Luminescent materials with dynamic responsiveness to external stimuli have attracted extensive attention for the development of advanced sensors and smart materials; however, self-healing capability is also of great importance for functional soft materials. An acid/base vapor reversibly triggered luminescence switch with self-healing ability is achieved by incorporating dynamic lanthanide metal-ligand (Ln-L) coordination into the soft polydimethylsiloxane polymer network. The emission color of the resultant luminescent material could be modulated by altering either the Eu3+/Tb3+ molar ratio or the excitation wavelength. The luminescence "On-Off" reversible switch is realized via direct alternating exposure to acid and base vapor, realizing reversible information encryption and decryption. The dynamic Ln-L cross-link as well as the hydrogen bond in the luminescent material endow it with excellent self-healing capability, high toughness, and stretchability. We believe this acid/base vapor-triggered self-healing switching strategy provides new insights for expanding the application range of luminescent materials.This study presents an important and efficient synthetic approach to 5,8-dibromo-2,11-di-tert-butylpicene (3), with multigram scale, which was then converted to a new series of picenophanes (6-10). The tub-shaped [2,2](5,8)picenophanediene 8 with two cis-ethylene linkers was explored using X-ray crystallography. The tub-to-tub inversion proceed through the successive bending of the linkers and the barrier for isopropyl-substituted derivative 10 was experimentally estimated to be 18.7 kcal/mol. Picenophanes with a large π-system and semi-rigid structure exhibited anomalous photophysical properties. The ethano-bridged picenophane shows the weak exciton delocalization while the cis-ethylene-bridged picenophane exhibits dual emission rendered by the weakly delocalized exciton and excimer. With the aid of the ultrafast time-resolved emission spectroscopy, the mechanism of the excimer formation is resolved, showing a unique behavior of two-state reversible reaction with fast structural deformation whose lifetime is around 20 ps at 298 K.

1 hr ago


The active metabolite of tamoxifen, 4-hydroxytamoxifen, functions as an anti-estrogen in breast cancer cells and thus inhibits proliferation. While tamoxifen continues to be successfully used to treat estrogen-dependent breast cancer, most patients receiving treatment will develop chemoresistance over time. Two commonly reported biomarkers of tamoxifen resistance are decreased expression of insulin-like growth factor 1 receptor (IGF-1R) and increased expression of epidermal growth factor receptor (EGFR). In prior work we have shown that these receptors facilitate chemoresistance and have unique regulatory functions measurable in resistant cell lines compared with nonresistant. Thus, we hypothesized that these receptors and a newly identified biomarker, integrin β1, may be used to search for the presence of resistant breast cancer cells within a population of cells that are sensitive to tamoxifen therapy. We tested this by designing a straightforward cell-labeling approach to measure differences in the receptor expression of resistant vs. sensitive cells cytometrically. Our results show that separation is possible when observing the expression of IGF-1R as well as integrin β1. Interestingly, we found no detectable difference in EGFR expression between tamoxifen resistant and -sensitive cells when measured with cytometry despite the fact that EGFR is upregulated in resistant cells. Our long-term goal is to utilize sorting to isolate tamoxifen resistant subpopulations of cells by receptor expression level. Isolating rare resistant cells that reside within a population of drug-sensitive cells will offer new insights into why chemoresistance occurs.
We aimed to replicate a prior Spanish study of medication adherence where logistic regression models provided highly significant odds ratios (ORs) for three continuous scores necessity, concern and the necessity-concern differential, and a dichotomous variable skeptical attitude. Adherence ORs in the necessity-concern framework were very strong in patients taking five or six medications.

The sample comprised consecutive adult psychiatric outpatients in Mendoza, Argentina. The necessity-concerns framework was assessed using a subscale of the Beliefs about Medicines Questionnaire. Adherence (yes/no) to prescribed psychiatric medications was assessed by the Sidorkiewicz adherence tool.

When compared with the Spanish sample, the Argentinian group (508 patients with 875 medications) was characterized by (1) significantly stronger adherence ORs with the necessity-concern framework, (2) significantly lower number of medications per patient and percentage of patients with marked psychiatric polypharmacy (≥4 medications), (3) though a higher number of medications still was significantly associated with poor adherence.

The Argentinian sample replicated the previous finding that patient beliefs regarding necessity and concern were associated with poor adherence to prescribed medications. Polypharmacy had an additive role decreasing adherence in both samples. https://www.selleckchem.com/products/ag-1478-tyrphostin-ag-1478.html In both samples, when prescribed ≥4 psychiatric medications, patients reported adherence to only two-third of the medications.
The Argentinian sample replicated the previous finding that patient beliefs regarding necessity and concern were associated with poor adherence to prescribed medications. Polypharmacy had an additive role decreasing adherence in both samples. In both samples, when prescribed ≥4 psychiatric medications, patients reported adherence to only two-third of the medications.Accurate numerical calculations of porosities and related properties are of importance when analyzing metal-organic frameworks (MOFs). We present porE, an open-source, general-purpose implementation to compute such properties and discuss all results regarding their sensitivity to numerical parameters. Our code combines the numerical efficiency of Fortran with the user-friendliness of Python. Three different approaches to calculate porosities are implemented in porE, and their advantages and drawbacks are discussed. In contrast to commonly used implementations, our approaches are entirely deterministic and do not require any stochastic averaging. In addition to the calculation of porosities, porE can calculate pore size distributions and offers the possibility to analyze pore windows. The underlying approaches are outlined, and pore windows are discussed concerning their impact on the analyzed porosities. Comparisons with reference values aim for a clear differentiation between void and accessible porosities, which we provide for a small benchmark set consisting of eight MOFs. In addition, our approaches are used for a bigger benchmark set containing 370 MOFs, where we determine linear relationships within our approaches as well as to reference values. We show how these relationships can be used to derive corrections to a give porosity approach, minimizing its mean error. As a highlight we show how complex workflows can be designed with a few lines of Python code using porE.
Dorsal root ganglion (DRG) stimulation is an effective treatment option for lower extremity complex regional pain syndrome and other focal pain conditions. However, the patient characteristics that may predict long-term outcomes have not been defined.

This was a retrospective observational study that included 93 patients who were implanted with a DRG stimulator at a single private practice institution. A variety of demographic data was collected. Follow-up results were reviewed from multiple time points more than 12 months. Patients were classified as either "responder" or "nonresponder" status using two different thresholds, "greater than or equal to 50% pain relief" and "greater than or equal to 80% pain relief."

A history of prior chronic opioid use was associated with significantly lower rates of responder status based on both a 50% pain relief threshold and 80% pain relief threshold at the one week to one month, three months, and 12-months visits.

This single-center retrospective study found patients prescribed chronic opioids at the time of DRG stimulator implantation had a higher likelihood of less than 50% pain relief and 80% pain relief at one month, three months, and 12 months follow-up visits.
This single-center retrospective study found patients prescribed chronic opioids at the time of DRG stimulator implantation had a higher likelihood of less than 50% pain relief and 80% pain relief at one month, three months, and 12 months follow-up visits.

Videos

12/18/2023

I understand why American Libertarians are skeptical of Javier Milei, I support that skepticism. But will he actually be able to implement his Libertarian economic order? Here are a few factors to consider.

Full Episode: https://tntvideo.podbean.com/e/jason-bassler-mark-gober-on-the-charlie-robinson-show-14-december-2023/

12/11/2023

Argentineans elected 53-year-old political outsider Javier Milei as their new president. Milei, an economist and self-described libertarian, pulled in nearly 56% of all votes counted in his runoff against left-wing rival opponent, Sergio Massa, completing one of the most unlikely presidential victories in modern history. On this episode of 360 View, Scottie Nell hughes asks her panel (Angela McArdle, Chair, Libertarian National Committee; Arn Menconi, Political Analyst; Esteban Carrillo, Journalist, The Cradle) about how the world is starting to pull away from the left leaning political views and are we seeing the rise of libertarian small government around the world?

11/16/2023

With the final election in Argentina right around the corner we have transited several relevant Retrosptectator videos into Spanish for our Argentine audience. Parte del equipo de Retrospectator es de #Argentina, lo que le proporciona una exposición de primera mano a los fracasos del socialismo y a cómo una civilización puede pasar de ser próspera a empobrecida por mil pequeñas mordidas y un gobierno expositivo de izquierda. Este video es más bien una colaboración de contenido entre yo, Joshua y Leonardo. Queremos que veas la historia de advertencia que Argentina se ha convertido desde la perspectiva argentina. Este video contrastará fuertemente con nuestro video de hace unas semanas, donde hablamos sobre el posible futuro de Argentina bajo #Javier #Milei. La elección es este domingo, así que estamos rompiendo aún más nuestro programa de lanzamientos con esta carga. Perdimos varias semanas porque Leonardo estaba ayudando en la campaña de Javier. Todos rezamos para que no se vuelva violento cuando los poderes establecidos pierdan la elección y potencialmente intenten mantener el control por la fuerza. #Milei2023 #JavierMilei

Circles

Sorry, no results were found.

Videos

12/18/2023

I understand why American Libertarians are skeptical of Javier Milei, I support that skepticism. But will he actually be able to implement his Libertarian economic order? Here are a few factors to consider.

Full Episode: https://tntvideo.podbean.com/e/jason-bassler-mark-gober-on-the-charlie-robinson-show-14-december-2023/

12/11/2023

Argentineans elected 53-year-old political outsider Javier Milei as their new president. Milei, an economist and self-described libertarian, pulled in nearly 56% of all votes counted in his runoff against left-wing rival opponent, Sergio Massa, completing one of the most unlikely presidential victories in modern history. On this episode of 360 View, Scottie Nell hughes asks her panel (Angela McArdle, Chair, Libertarian National Committee; Arn Menconi, Political Analyst; Esteban Carrillo, Journalist, The Cradle) about how the world is starting to pull away from the left leaning political views and are we seeing the rise of libertarian small government around the world?

11/16/2023

With the final election in Argentina right around the corner we have transited several relevant Retrosptectator videos into Spanish for our Argentine audience. Parte del equipo de Retrospectator es de #Argentina, lo que le proporciona una exposición de primera mano a los fracasos del socialismo y a cómo una civilización puede pasar de ser próspera a empobrecida por mil pequeñas mordidas y un gobierno expositivo de izquierda. Este video es más bien una colaboración de contenido entre yo, Joshua y Leonardo. Queremos que veas la historia de advertencia que Argentina se ha convertido desde la perspectiva argentina. Este video contrastará fuertemente con nuestro video de hace unas semanas, donde hablamos sobre el posible futuro de Argentina bajo #Javier #Milei. La elección es este domingo, así que estamos rompiendo aún más nuestro programa de lanzamientos con esta carga. Perdimos varias semanas porque Leonardo estaba ayudando en la campaña de Javier. Todos rezamos para que no se vuelva violento cuando los poderes establecidos pierdan la elección y potencialmente intenten mantener el control por la fuerza. #Milei2023 #JavierMilei

Posts

32 mins ago


We further assessed the functions of non-essential CaRSC subunits, showing that the novel subunit Nri1 and the bromodomain subunit Rsc4 play roles in filamentation and stress responses; and also interacted at the genetic level to regulate cell viability. Consistent with these roles, Rsc4 is required for full virulence of C. albicans in the murine model of systemic infection. Taken together, our data builds the first comprehensive study of the composition and roles of RSC in C. albicans, showing both conserved and distinct features compared to model fungal systems. The study illuminates how C. albicans uses RSC-dependent transcriptional regulation to respond to environmental signals and drive survival fitness and virulence in mammals.25-Hydroxyvitamin D [25(OH)D] has been reported to be associated with several chronic liver diseases. The relationship between 25(OH)D and autoimmune hepatitis (AIH) pathogenesis is incompletely understood. We investigated the association of serum total and free 25(OH)D levels with necroinflammatory activity and cytokine levels in 66 patients with AIH diagnosed in our hospital. The median age at AIH diagnosis was 57 years, and the malefemale ratio was 759. The median serum total 25(OH)D level in therapy-naïve patients with AIH was 14.2 ng/mL (interquartile range [IQR], 11.4-17.9 ng/mL). Of the 66 patients with AIH, 36 had serum total 25(OH)D levels of less then 15 ng/mL and were considered to have vitamin D deficiency, and 30 had serum total 25(OH)D levels of ≥ 15 ng/mL. Patients with acute-onset AIH had significantly lower serum total 25(OH)D levels than those with chronic-onset AIH. In particular, serum total 25(OH)D levels were significantly lower in patients with severe forms of AIH. Furthermore, the serum total 25(OH)D level was positively correlated with the serum albumin level and prothrombin time and negatively correlated with the serum total bilirubin level and necroinflammatory activity in AIH. Multivariate logistic regression analysis showed that the serum total 25(OH)D level was an independent factor for severe necroinflammatory activity. Interestingly, AIH patients with serum total 25(OH)D levels of less then 15 ng/mL had higher levels of inflammatory cytokines such as interferon-γ and interleukin-33. Free 25(OH)D levels were correlated with total 25(OH)D levels, and the percentage of free 25(OH)D was significantly associated with necroinflammatory activity. In conclusion, 25(OH)D deficiency may play an important role in predicting AIH severity via inflammatory cytokine production.We showed the results of the first long-term analysis (1987-2019) of pesticide (herbicides, fungicides and insecticides) impact in the Rolling Pampa, one of the main agricultural areas of Argentina. Using a clear and meaningful tool, based not only on acute toxicity but also on scaling up the results to total sown area, we identified time trends for both pesticide impact and the ecoefficiency of modal pesticide profiles. By the end of the time series, soybean showed a pesticide impact four times greater than maize crop in the studied area. However, the time trend in the subperiod (2012-2019) showed a sustainable pattern of pesticide use in soybean crop, with an improvement in its ecoefficiency. Oppositely, maize showed a relatively constant ecoefficiency value during most of the time series, suggesting a possible path towards an unsustainable cropping system. Findings from this study suggest that some efforts have to be made to improve the pest management decisions towards a more efficient pesticide profiles in maize crop and to keep improving the ecotoxicity pesticide profile in soybean crops because of its large sown area in the studied area.
Cervical Cancer is the leading cause of cancer-related deaths among Ethiopian women. Despite many interventions were conducted, there is low uptake of cervical cancer screening services. https://www.selleckchem.com/products/gsk484-hcl.html Also, limited evidence was available on the women's intention and its predictors towards cervical cancer screening. Therefore, this study was aimed at determining the intention and predicators of behavioral intention toward cervical cancer screening.

A cross-sectional study was conducted in the Gomma district, Jimma, Ethiopia from August 1-30, 2019. The total sample sizes were 422 and a systematic random sampling technique was employed to select the samples. Data were collected through interviews using a structured questionnaire guide. Data were entered in epidata, and exported and analyzed using SPSS version 20.0 software. Descriptive, correlation, and multicollinearity analysis were done. Also, simple and multiple linear regression analysis were performed to identify the predictors for behavioral intention. The p-value&Radiotherapy plays a major role in the curative treatment of head and neck cancer, either as a single modality therapy, or in combination with surgery or chemotherapy, or both. Despite advances to limit radiation-induced side-effects, the major salivary glands are often affected. This frequently leads to hyposalivation which causes an increased risk for xerostomia, dental caries, mucositis, and malnutrition culminating in a significant impact on patients' quality of life. Previous research demonstrated that loss of salivary function is associated with a decrease in polarity regulators and an increase in nuclear Yap localization in a putative stem and progenitor cell (SPC) population. Yap activation has been shown to be essential for regeneration in intestinal injury models; however, the highest levels of nuclear Yap are observed in irradiated salivary SPCs that do not regenerate the gland. Thus, elucidating the inputs that regulate nuclear Yap localization and determining the role that Yap plays within the entire tissue following radiation damage and during regeneration is critical. In this study, we demonstrate that radiation treatment increases nuclear Yap localization in acinar cells and Yap-regulated genes in parotid salivary tissues. Conversely, administration of insulin-like growth factor 1 (IGF1), known to restore salivary function in mouse models, reduces nuclear Yap localization and Yap transcriptional targets to levels similar to untreated tissues. Activation of Rho-associated protein kinase (ROCK) using calpeptin results in increased Yap-regulated genes in primary acinar cells while inhibition of ROCK activity (Y-27632) leads to decreased Yap transcriptional targets. These results suggest that Yap activity is dependent on ROCK activity and provides new mechanistic insights into the regulation of radiation-induced hyposalivation.

43 mins ago


A synthetic strategy to fused bicyclic piperidines-building blocks for medicinal chemistry-is developed. The key step was an intramolecular [2 + 2]-photocyclization. The photochemical step was performed on a gram scale. Crystallographic analysis of the obtained compounds revealed that they occupy a novel chemical space and can be considered as elongated analogues of 3-substituted piperidines.The recent "US-China trade war" has aroused concern over trade-related environmental impacts. This study built a multiregional computable general equilibrium model to simulate environmental impacts of the "US-China trade war" under different scenarios of tariff and nontariff barriers and the battlefield spreading ranges. The present study found that although the trade war will cause a global economic downturn, which will seemingly reduce environmental pressure globally, global carbon emissions are expected to increase rather than decline. On the one hand, the CO2 emission increase caused by land-use changes in Brazil and Argentina will far exceed the emission reduction because of decreased global production. On the other hand, some countries/economies especially those developing countries such as Vietnam, Russia, and India will face emission increases driven by scale effects. Countries such as Korea, the UK, and France will enjoy a reduction in emissions driven by structural effects. China and the US will face a reduction in production and CO2 emissions, but their CO2 emission intensities will rise. The results remind us that as global production and supply chains are formed, it is important to closely monitor trade-related environmental impacts. Efforts should be made to balance the interests of trade and the environment.Isolating isomorphic compounds of tetravalent actinides (i.e., ThIV, UIV, NpIV, and PuIV) improve our understanding of the bonding behavior across the series, in addition to their relationship with tetravalent transition metals (Zr and Hf) and lanthanides (Ce). Similarities between these tetravalent metals are particularly illuminated in their hydrolysis and condensation behavior in aqueous systems, leading to polynuclear clusters typified by the hexamer [MIV6O4(OH)4]12+ building block. Prior studies have shown the predominance and coexistence of smaller species for ThIV (monomers, dimers, and hexamers) and larger species for UIV, NpIV, and PuIV (including 38-mers and 70-mers). We show here that aqueous uranium(IV) sulfate also displays behavior similar to that of ThIV (and ZrIV) in its isolated solid-phase and solution speciation. Two single-crystal X-ray structures are described a dihydroxide-bridged dimer (U 2 ) formulated as U2(OH)2(SO4)3(H2O)4 and a monomer-linked hexamer framework (U-U 6 ) as (U(H2O)3.5)2U6O4(OH)4(SO4)10(H2O)9. These structures are similar to those previously described for ThIV. Moreover, cocrystallization of monomer and dimer and of dimer and monomer-hexamer phases for both ThIV (prior) and UIV (current) indicates the coexistence of these species in solution. https://www.selleckchem.com/products/pfi-2.html Because it was not possible to effectively study the sulfate-rich solutions via X-ray scattering from which U 2 and U-U 6 crystallized, we provide a parallel solution speciation study in low sulfate conditions, as a function of the pH. Raman spectroscopy, UV-vis spectroscopy, and small-angle X-ray scattering of these show decreasing sulfate binding, increased hydrolysis, increased species size, and increased complexity, with increasing pH. This study describes a bridge across the first half the actinide series, highlighting UIV similarities to ThIV, in addition to the previously known similarities to the transuranic elements.A new mechanism of allostery in proteins, based on charge rather than structure, is reported. We demonstrate that dynamic redistribution of charge within a protein can control its function and affect its interaction with a binding partner. In particular, the association of an antibody with its target protein antigen is studied. Dynamic charge shifting within the antibody during its interaction with the antigen is enabled by its binding to a metallic surface that serves as a source for electrons. The kinetics of antibody-antigen association are enhanced when charge redistribution is allowed, even though charge injection happens at a position far from the antigen binding site. This observation points to charge-reorganization allostery, which should be operative in addition or parallel to other mechanisms of allostery, and may explain some current observations on protein interactions.Luminescent materials with dynamic responsiveness to external stimuli have attracted extensive attention for the development of advanced sensors and smart materials; however, self-healing capability is also of great importance for functional soft materials. An acid/base vapor reversibly triggered luminescence switch with self-healing ability is achieved by incorporating dynamic lanthanide metal-ligand (Ln-L) coordination into the soft polydimethylsiloxane polymer network. The emission color of the resultant luminescent material could be modulated by altering either the Eu3+/Tb3+ molar ratio or the excitation wavelength. The luminescence "On-Off" reversible switch is realized via direct alternating exposure to acid and base vapor, realizing reversible information encryption and decryption. The dynamic Ln-L cross-link as well as the hydrogen bond in the luminescent material endow it with excellent self-healing capability, high toughness, and stretchability. We believe this acid/base vapor-triggered self-healing switching strategy provides new insights for expanding the application range of luminescent materials.This study presents an important and efficient synthetic approach to 5,8-dibromo-2,11-di-tert-butylpicene (3), with multigram scale, which was then converted to a new series of picenophanes (6-10). The tub-shaped [2,2](5,8)picenophanediene 8 with two cis-ethylene linkers was explored using X-ray crystallography. The tub-to-tub inversion proceed through the successive bending of the linkers and the barrier for isopropyl-substituted derivative 10 was experimentally estimated to be 18.7 kcal/mol. Picenophanes with a large π-system and semi-rigid structure exhibited anomalous photophysical properties. The ethano-bridged picenophane shows the weak exciton delocalization while the cis-ethylene-bridged picenophane exhibits dual emission rendered by the weakly delocalized exciton and excimer. With the aid of the ultrafast time-resolved emission spectroscopy, the mechanism of the excimer formation is resolved, showing a unique behavior of two-state reversible reaction with fast structural deformation whose lifetime is around 20 ps at 298 K.

1 hr ago


The active metabolite of tamoxifen, 4-hydroxytamoxifen, functions as an anti-estrogen in breast cancer cells and thus inhibits proliferation. While tamoxifen continues to be successfully used to treat estrogen-dependent breast cancer, most patients receiving treatment will develop chemoresistance over time. Two commonly reported biomarkers of tamoxifen resistance are decreased expression of insulin-like growth factor 1 receptor (IGF-1R) and increased expression of epidermal growth factor receptor (EGFR). In prior work we have shown that these receptors facilitate chemoresistance and have unique regulatory functions measurable in resistant cell lines compared with nonresistant. Thus, we hypothesized that these receptors and a newly identified biomarker, integrin β1, may be used to search for the presence of resistant breast cancer cells within a population of cells that are sensitive to tamoxifen therapy. We tested this by designing a straightforward cell-labeling approach to measure differences in the receptor expression of resistant vs. sensitive cells cytometrically. Our results show that separation is possible when observing the expression of IGF-1R as well as integrin β1. Interestingly, we found no detectable difference in EGFR expression between tamoxifen resistant and -sensitive cells when measured with cytometry despite the fact that EGFR is upregulated in resistant cells. Our long-term goal is to utilize sorting to isolate tamoxifen resistant subpopulations of cells by receptor expression level. Isolating rare resistant cells that reside within a population of drug-sensitive cells will offer new insights into why chemoresistance occurs.
We aimed to replicate a prior Spanish study of medication adherence where logistic regression models provided highly significant odds ratios (ORs) for three continuous scores necessity, concern and the necessity-concern differential, and a dichotomous variable skeptical attitude. Adherence ORs in the necessity-concern framework were very strong in patients taking five or six medications.

The sample comprised consecutive adult psychiatric outpatients in Mendoza, Argentina. The necessity-concerns framework was assessed using a subscale of the Beliefs about Medicines Questionnaire. Adherence (yes/no) to prescribed psychiatric medications was assessed by the Sidorkiewicz adherence tool.

When compared with the Spanish sample, the Argentinian group (508 patients with 875 medications) was characterized by (1) significantly stronger adherence ORs with the necessity-concern framework, (2) significantly lower number of medications per patient and percentage of patients with marked psychiatric polypharmacy (≥4 medications), (3) though a higher number of medications still was significantly associated with poor adherence.

The Argentinian sample replicated the previous finding that patient beliefs regarding necessity and concern were associated with poor adherence to prescribed medications. Polypharmacy had an additive role decreasing adherence in both samples. https://www.selleckchem.com/products/ag-1478-tyrphostin-ag-1478.html In both samples, when prescribed ≥4 psychiatric medications, patients reported adherence to only two-third of the medications.
The Argentinian sample replicated the previous finding that patient beliefs regarding necessity and concern were associated with poor adherence to prescribed medications. Polypharmacy had an additive role decreasing adherence in both samples. In both samples, when prescribed ≥4 psychiatric medications, patients reported adherence to only two-third of the medications.Accurate numerical calculations of porosities and related properties are of importance when analyzing metal-organic frameworks (MOFs). We present porE, an open-source, general-purpose implementation to compute such properties and discuss all results regarding their sensitivity to numerical parameters. Our code combines the numerical efficiency of Fortran with the user-friendliness of Python. Three different approaches to calculate porosities are implemented in porE, and their advantages and drawbacks are discussed. In contrast to commonly used implementations, our approaches are entirely deterministic and do not require any stochastic averaging. In addition to the calculation of porosities, porE can calculate pore size distributions and offers the possibility to analyze pore windows. The underlying approaches are outlined, and pore windows are discussed concerning their impact on the analyzed porosities. Comparisons with reference values aim for a clear differentiation between void and accessible porosities, which we provide for a small benchmark set consisting of eight MOFs. In addition, our approaches are used for a bigger benchmark set containing 370 MOFs, where we determine linear relationships within our approaches as well as to reference values. We show how these relationships can be used to derive corrections to a give porosity approach, minimizing its mean error. As a highlight we show how complex workflows can be designed with a few lines of Python code using porE.
Dorsal root ganglion (DRG) stimulation is an effective treatment option for lower extremity complex regional pain syndrome and other focal pain conditions. However, the patient characteristics that may predict long-term outcomes have not been defined.

This was a retrospective observational study that included 93 patients who were implanted with a DRG stimulator at a single private practice institution. A variety of demographic data was collected. Follow-up results were reviewed from multiple time points more than 12 months. Patients were classified as either "responder" or "nonresponder" status using two different thresholds, "greater than or equal to 50% pain relief" and "greater than or equal to 80% pain relief."

A history of prior chronic opioid use was associated with significantly lower rates of responder status based on both a 50% pain relief threshold and 80% pain relief threshold at the one week to one month, three months, and 12-months visits.

This single-center retrospective study found patients prescribed chronic opioids at the time of DRG stimulator implantation had a higher likelihood of less than 50% pain relief and 80% pain relief at one month, three months, and 12 months follow-up visits.
This single-center retrospective study found patients prescribed chronic opioids at the time of DRG stimulator implantation had a higher likelihood of less than 50% pain relief and 80% pain relief at one month, three months, and 12 months follow-up visits.


e., no cases of early abortion and only 1 case of late abortion, versus 14 and 9 cases in pregnancies with 0-5 transfusions, respectively. Despite advances in the management of SCD, pregnant women with SCD (particularly those with HbSS) are at a high risk for maternal and fetal complications, even though they are followed in reference centers.

The lower risk of intrauterine fetal death for those women who received more transfusions throughout pregnancy observed in the current study leads us once more to raise the need for prospective, multicenter, randomized trials to determine whether the potential benefits balance the risks of prophylactic transfusions.
The lower risk of intrauterine fetal death for those women who received more transfusions throughout pregnancy observed in the current study leads us once more to raise the need for prospective, multicenter, randomized trials to determine whether the potential benefits balance the risks of prophylactic transfusions.Parkinson's is a neurodegenerative disease, characterized by the loss of dopaminergic neurons, cholinergic alterations and oxidative damages. Lutein is widely known by its antioxidants properties. In the present study, we investigated whether lutein-loaded nanoparticles protects against locomotor damage and neurotoxicity induced by Parkinson's disease model in Drosophila melanogaster, as well as possible mechanisms of action. First, the nanoparticles were characterized by physicochemical methods, demonstrating that water affinity was improved by the encapsulation of lutein into the polymeric encapsulant matrix. The fruit flies of 1-4 days old were divided into four groups and exposed to a standard diet (control), a diet containing either rotenone (500 μM), lutein-loaded nanoparticles (6 μM) or rotenone (500 μM) and lutein-loaded nanoparticles (6 μM) for 7 days. The survival percentage was assessed, the flies were submitted to negative geotaxis, open field tasks and the determination of dopamine levels, tyrosine hydroxylase (TH) and acetylcholinesterase activities and oxidative stress indicators (superoxide dismutase, catalase, thiobarbituric acid reactive substances and glutathione S-transferase) were carried out. The exposure to lutein-loaded nanoparticles protected against locomotor damage and the decrease survival rate induced by rotenone, besides, it restored the dopamine levels, TH and acetylcholinesterase activities and oxidative stress indicators. These results provide evidence that lutein-loaded nanoparticles are an alternative treatment for rotenone-induced damage, and suggest the involvement of dopaminergic and cholinergic system and oxidative stress.When subjected to molecular study, species of digeneans believed to be cosmopolitan are usually found to consist of complexes of species with narrower distributions. We present molecular and morphological evidence of transcontinental distributions in two species of Apharyngostrigea Ciurea, 1924, based on samples from Africa and the Americas. Sequences of cytochrome c oxidase I and, in some samples, internal transcribed spacer, revealed Apharyngostrigea pipientis (Faust, 1918) in Tanzania (first known African record), Argentina, Brazil, USA and Canada. Sequences from A. pipientis also match previously published sequences identified as Apharyngostrigea cornu (Zeder, 1800) originating in Mexico. Hosts of A. pipientis surveyed include definitive hosts from the Afrotropic, Neotropic and Nearctic, as well as first and second intermediate hosts from the Americas, including the type host and type region. In addition, metacercariae of A. pipientis were obtained from experimentally infected Poecilia reticulata, the first known record of this parasite in a non-amphibian second intermediate host. Variation in cytochrome c oxidase I haplotypes in A. pipientis is consistent with a long established, wide-ranging species with moderate genetic structure among Nearctic, Neotropic and Afrotropic regions. We attribute this to natural dispersal by birds and find no evidence of anthropogenic introductions of exotic host species. Sequences of CO1 and ITS from adult Apharyngostrigea simplex (Johnston, 1904) from Egretta thula in Argentina matched published data from cercariae from Biomphalaria straminea from Brazil and metacercariae from Cnesterodon decemmaculatus in Argentina, consistent with previous morphological and life-cycle studies reporting this parasite-originally described in Australia-in South America. Analyses of the mitochondrial genome and rDNA operon from A. pipientis support prior phylogenies based on shorter markers showing the Strigeidae Railliet, 1919 to be polyphyletic.
In recent years, the use of outpatient parenteral antimicrobial therapy (OPAT) has increased, resulting in the need to ensure its rational and adequate utilization. This article describes the implementation of an antimicrobial stewardship program in the OPAT setting by a Health Maintenance Organization (HMO) and its results.

An infectious disease (ID) physician made routine assessments of all home care parenteral antimicrobial requests from February to December 2019. Information on diagnosis, renal function, weight, previous antimicrobials, and microbiology were gathered during remote evaluations. Prescription changes recommended by the ID specialist were not mandatory, but implemented by the primary provider as accepted. Antibiotic consumption data was analyzed from January 2018 to December 2019. An active screening was conducted for treatment failures two or more treatment course requirements, or death within 15 days of the evaluation were reexamined.

A total of 506 antimicrobial requests were assesset, was effective and safe in the OPAT setting.
Outpatient antimicrobial stewardship, through remote assessment by an ID specialist, was effective and safe in the OPAT setting.
Cerebellar arteriovenous malformations (cAVMs) are rare and challenging lesions with an aggressive natural history. The mechanisms whereby a patient can worsen clinically after a supratentorial AVM resection include an acute alteration in cerebral hemodynamics, which is a known cause of postoperative hyperemia, edema and/or hemorrhage. These phenomena has not been described for cAVMS. Moreover, the underlying pathophysiology of edema and hemorrhage after AVM resection still remains controversial.

We report a patient that presented an abrupt neurological deterioration after cAVM surgical resection. https://www.selleckchem.com/products/jzl184.html Emergent external ventricular drainage to treat incipient hydrocephalus only partially reverted the patient's deterioration. Consecutive post-surgery CT images revealed fourth ventricle compression secondary to cerebellar swelling that concurred with a new neurological deterioration. Densitometric analysis was performed in these CT images to reveal the nature of these changes as well as their evolution over time.

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We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013-2017. Of 303 cases reported during that period, 133 (44%) were included in this study. The median time between onset of illness and diagnosis of SFTS shortened, from 11.5 to 3.0 days, but the case-fatality rate remained high, at 27%. In 64 patients (48%), a close contact with companion animals was reported within 2 weeks of disease onset. Of these 64 patients, 40 were surveyed further, and we confirmed that 3 had direct contact with body fluids of ill companion animals; 2 had direct contact with the saliva of an ill feral cat or pet dog. These patients reported no history of tick bite, suggesting that ill companion animals might be a source of SFTS virus transmission. Direct contact with the body fluids of ill companion animals should be avoided.Bloodstream infections caused by uncommon or novel fungal species are challenging to identify and treat. We report a series of cases of fungemia due to a rare basidiomycete yeast, Dirkmeia churashimaensis, in neonatal patients in India. Whole-genome sequence typing demonstrated that the patient isolates were genetically indistinguishable, indicating a single-source infection.From November 2018 through July 2019, an outbreak of Rift Valley fever in humans occurred in Mayotte, France; 142 cases were confirmed. Exposure to animals or their biological fluid was reported by 73% of patients. Health authorities have been implementing control measures, including veterinary surveys, vector control interventions, and prevention measures.A 41-year-old man from Son La Province, Vietnam, sought care for disseminated prurigo-like skin lesions from which nematode larvae were emerging. We morphologically and molecularly identified the larvae as Oxyspirura sp. Our findings confirm this nematode species as a zoonotic pathogen for emerging disease.Recent seroprevalence studies in animals detected Rocio virus in regions of Brazil, indicating risk for re-emergence of this pathogen. We identified Rocio virus RNA in samples from 2 human patients for whom dengue fever was clinically suspected but ruled out by laboratory findings. Testing for infrequent flavivirus infections should expedite diagnoses.We detected 3 Bartonella species in wild rabbit fleas from Colorado, USA B. vinsonii subsp. berkhoffii (n = 16), B. alsatica (n = 5), and B. rochalimae (n = 1). Our results support the establishment of the zoonotic agent B. alsatica in North America.Ebola virus (EBOV) is a highly pathogenic zoonotic virus for which the reservoir host has not been identified. https://www.selleckchem.com/products/LY2228820.html To study the role of dogs as potential hosts, we screened 300 serum samples from dogs in Sierra Leone and found EBOV neutralizing antibodies in 12, suggesting their susceptibility to natural infection.Shigellosis outbreaks caused by Shigella with decreased susceptibility to azithromycin (DSA-Shigella) among men who have sex with men (MSM) have been reported worldwide. We describe sexual health indicators and antimicrobial drug resistance for shigellosis cases in Minnesota, USA. We analyzed a sample of isolates received during 2012-2015 and cross-referenced cases with the Minnesota Department of Health Sexually Transmitted Disease Database to ascertain patients' HIV status and recent chlamydia, gonorrhea, and syphilis infections. Of 691 Shigella isolates, 46 (7%) were DSA-Shigella; 91% of DSA-Shigella patients were men, of whom 60% were living with HIV. Among men, those with DSA-Shigella infection had greater odds of living with HIV, identifying as MSM, or having a recent diagnosis of a sexually transmitted disease. DSA-Shigella was associated with MSM, HIV infection, and recent sexually transmitted disease. To decrease spread of DSA-Shigella, interventions targeted at communities at high risk are needed.Andes virus is unique among hantaviruses because it can be transmitted from person to person. This mechanism was previously supported by epidemiologic data and genetic evidence based only on partial sequences. We used full-length virus sequencing to confirm person-to-person transmission of this virus in a cluster of 3 cases in Argentina in 2014.During April-June 2014 in a malaria-endemic rural community close to the city of Iquitos in Peru, we detected evidence of Guaroa virus (GROV) infection in 14 febrile persons, of whom 6 also had evidence of Plasmodium vivax malaria. Cases were discovered through a long-term febrile illness surveillance network at local participating health facilities. GROV cases were identified by using a combination of seroconversion and virus isolation, and malaria was diagnosed by thick smear and PCR. GROV mono-infections manifested as nonspecific febrile illness and were clinically indistinguishable from GROV and P. vivax co-infections. This cluster of cases highlights the potential for GROV transmission in the rural Peruvian Amazon, particularly in areas where malaria is endemic. Further study of similar areas of the Amazon may provide insights into the extent of GROV transmission in the Amazon basin.Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013-2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain23F-ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure.