Trends in prostate cancer incidence among Black men in the Caribbean and the United States.

BACKGROUND: Prostate cancer incidence is highest for Black men of the African diaspora in the United States and Caribbean. Recent changes in recommendations for prostate cancer screening have been shown to decrease overall prostate cancer incidence and increase the likelihood of late stage disease. However, it is unclear how trends in prostate cancer characteristics among high risk Black men differ by geographic region during the changes in screening recommendations. METHODS: In this study, we used population-based prostate cancer registry data to describe age-adjusted prostate cancer incidence trends from 2008 to 2015 among Black men from six geographic regions. We obtained data on incident Black prostate cancer patients from six cancer registries (in the United States: Florida, Alabama, Pennsylvania, and New York; and in the Caribbean: Guadeloupe and Martinique). After age standardization, we used descriptive analyses to compare the demographics and tumor characteristics by cancer registry site. The Joinpoint regression program was used to compare the trends in incidence by site. RESULTS: A total of 59,246 men were analyzed. We found the highest incidence rates (per 100,000) for prostate cancer in the Caribbean countries (181.99 in Martinique and 176.62 in Guadeloupe) and New York state (178.74). Incidence trends decreased significantly over time at all sites except Martinique, which also showed significantly increasing rates of late stage (III/IV) and Gleason score 7+ tumors. CONCLUSIONS: We observed significant differences in prostate cancer incidence trends among Black men after major changes prostate screening recommendations. Future studies will examine the factors that differentially influence prostate cancer trends among the African diaspora.

Microwave Irradiation as a Powerful Tool for the Preparation of n-Type Benzotriazole Semiconductors with Applications in Organic Field-Effect Transistors.

In this work, as an equivocal proof of the potential of microwave irradiation in organic synthesis, a complex pyrazine-decorated benzotriazole derivative that is challenging to prepare under conventional conditions has been obtained upon microwave irradiation, thus efficiently improving the process and yields, dramatically decreasing the reaction times and resulting in an environmentally friendly synthetic procedure. In addition, this useful derivative could be applied in organic electronics, specifically in organic field-effect transistors (OFETs), exhibiting the highest electron mobilities reported to date for benzotriazole discrete molecules, of around 10-2 cm2V-1s-1.

On-Demand Hydrophobic Drug Release Based on Microwave-Responsive Graphene Hydrogel Scaffolds.

Electromagnetically driven drug delivery systems stand out among stimulus-responsive materials due to their ability to release cargo on demand by remote stimulation, such as light, near infrared (NIR) or microwave (MW) radiation. MW-responsive soft materials, such as hydrogels, generally operate at 2.45 GHz frequencies, which usually involves rapid overheating of the scaffold and may affect tissue surrounding the target location. In contrast, 915 MHz MW penetrate deeper tissues and are less prone to induce rapid overheating. In order to circumvent these limitations, we present here for the first time a graphene-based hydrogel that is responsive to MW irradiation of ν=915 MHz. This system is a candidate soft scaffold to deliver a model hydrophobic drug. The graphene present in the hydrogel acts as a heat-sink and avoids overheating of the scaffold upon MW irradiation. In addition, the microwave trigger stimulates the in vitro delivery of the model drug, thus suggesting a remote and deep-penetrating means to deliver a drug from a delivery reservoir. Moreover, the MW-triggered release of drug was observed to be enhanced under acidic conditions, where the swelling state is maximum due to the swelling-induced pH-responsiveness of the hydrogel. The hybrid composite described here is a harmless means to deliver remotely a hydrophobic drug on demand with a MW source of 915 MHz. Potential use in biomedical applications were evaluated by cytotoxicity tests.

Extended Alkenyl and Alkynyl Benzotriazoles with Enhanced Two-Photon Absorption Properties as a Promising Alternative to Benzothiadiazoles.

A series of donor-π-acceptor-π-donor (D-π-A-π-D) benzoazole dyes with 2H-benzo[d][1,2,3]triazole or BTD cores have been prepared and their photophysical properties characterized. The properties of these compounds display remarkable differences, mainly as a result of the electron-donor substituent. Dyes with the best properties have visible-light absorption over λ=400 nm, large Stokes shifts in the range of about 3500-6400 cm-1 , and good fluorescence emission with quantum yields of up to 0.78. The two-photon absorption properties were also studied to establish the relationship between structure and properties in the different compounds synthesized. These results provided cross sections of up to 1500 GM, with a predominance of S2 ←S0 transitions and a high charge-transfer character. Time-dependent DFT calculations supported the experimental results.

Photoinduced Palladium-Catalyzed Negishi Cross-Couplings Enabled by the Visible-Light Absorption of Palladium-Zinc Complexes.

A visible-light-induced Negishi cross-coupling is enabled by the activation of a Pd0 -Zn complex. With this photocatalytic method, the scope of deactivated aryl halides that can be employed in the Negishi coupling was significantly expanded. NMR experiments conducted in the presence and absence of light confirmed that the formation of the palladium-zinc complex is key for accelerating the oxidative addition step.

Functionomics of NCC mutations in Gitelman syndrome using a novel mammalian cell-based activity assay.

Gitelman syndrome (GS) is an autosomal recessive salt-wasting tubular disorder resulting from loss-of-function mutations in the thiazide-sensitive NaCl cotransporter (NCC). Functional analysis of these mutations has been limited to the use of Xenopus laevis oocytes. The aim of the present study was, therefore, to analyze the functional consequences of NCC mutations in a mammalian cell-based assay, followed by analysis of mutated NCC protein expression as well as glycosylation and phosphorylation profiles using human embryonic kidney (HEK) 293 cells. NCC activity was assessed with a novel assay based on thiazide-sensitive iodide uptake in HEK293 cells expressing wild-type or mutant NCC (N59I, R83W, I360T, C421Y, G463R, G731R, L859P, or R861C). All mutations caused a significantly lower NCC activity. Immunoblot analysis of the HEK293 cells revealed that 1) all NCC mutants have decreased NCC protein expression; 2) mutant N59I, R83W, I360T, C421Y, G463R, and L859P have decreased NCC abundance at the plasma membrane; 3) mutants C421Y and L859P display impaired NCC glycosylation; and 4) mutants N59I, R83W, C421Y, C731R, and L859P show affected NCC phosphorylation. In conclusion, we developed a mammalian cell-based assay in which NCC activity assessment together with a profiling of mutated protein processing aid our understanding of the pathogenic mechanism of the NCC mutations.

Expression of CHRFAM7A and CHRNA7 in neuronal cells and postmortem brain of HIV-infected patients: considerations for HIV-associated neurocognitive disorder.

Despite the recent advances in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1) remains a global health threat. HIV-1 affects the central nervous system by releasing viral proteins that trigger neuronal death and neuroinflammation, and promotes alterations known as HIV-associated neurocognitive disorders (HAND). This disorder is not fully understood, and no specific treatments are available. Recently, we demonstrated that the HIV-1 envelope protein gp120IIIB induces a functional upregulation of the α7-nicotinic acetylcholine receptor (α7) in neuronal cells. Furthermore, this upregulation promotes cell death that can be abrogated with receptor antagonists, suggesting that α7 may play an important role in the development of HAND. The partial duplication of the gene coding for the α7, known as CHRFAM7A, negatively regulates α7 expression but its role in HIV infection has not been studied. Hence, we studied both CHRNA7 and CHRFAM7A regulation patterns in various gp120IIIB in vitro conditions. In addition, we measured CHRNA7 and CHRFAM7A expression levels in postmortem brain samples from patients suffering from different stages of HAND. Our results demonstrate the induction of CHRNA7 expression accompanied by a significant downregulation of CHRFAM7A in neuronal cells when exposed to pathophysiological concentrations of gp120IIIB. Our results suggest a dysregulation of CHRFAM7A and CHRNA7 expressions in the basal ganglia from postmortem brain samples of HIV+ subjects and expand the current knowledge about the consequences of HIV infection in the brain.

Effects of outdoor cultures on the growth and lipid production of Phaeodactylum tricornutum using closed photobioreactors.

One of the principal challenges for large scale production of microalgae is the high costs of biomass production. Aiming for minimize this problem, microalgal biodiesel production should focus on outdoors cultures, using available solar light and allowing lower energy cost process. Testing species that proved to be common and easy to culture may be a good approach in this process. The present work reports indoor-outdoor cultures of Phaeodactylum tricornutum using different bioreactors types, using cell growth, biochemical composition, and the profiles of the fatty acids produced as the parameters to test the optimization processes. The results show that the use of outdoor cultures is a good choice to obtain P. tricornutum biomass with a good potential for biodiesel production. The microalgae produced reached better growth efficiency, major lipid content and showed an increment in the percentage of saturated fatty acids (required on the biodiesel production) respect indoor cultures. These results are important to show the relevance of using outdoor cultures as a way to improve the efficiency and the energetic balance of the biodiesel production with P. tricornutum algae.

4-Aryl-3,5-bis(arylethynyl)aryl-4H-1,2,4-triazoles: multitasking skeleton as a self-assembling unit.

The synthesis of a series of 4-aryl-3,5-bis(arylethynyl)aryl-4H-1,2,4-triazoles derivatives is reported and the influence exerted by peripheral substitution on the morphology of the aggregates generated from these 1,2,4-triazoles is investigated by SEM imaging. The presence of paraffinic side chains results in long fibrillar supramolecular structures, but unsubstituted triazoles self-assemble into thinner ribbons and needle-like aggregates. The crystals obtained from methoxy-substituted triazoles have been utilised to elaborate a model that helps to justify aggregation of the investigated 1,2,4-triazoles, in which the operation of arrays of C-H⋅⋅⋅π non-covalent interactions plays a significant role. The results presented herein demonstrate the ability of simple molecules to behave as multitasking scaffolds with different properties, depending on peripheral substitution. Thus, although 1,2,4-triazoles without long paraffinic side chains exhibit optical waveguiding behaviour, triazoles endowed with peripheral paraffinic side chains exhibit hexagonal columnar mesomorphism.

Histopathological changes in third-instar and adult Anastrepha ludens (Diptera: Tephritidae) after in vitro heat treatment.

The Mexican fruit fly, Anastrepha ludens Loew (Diptera: Tephritidae), is one of the most harmful pests of mango causing direct damage by oviposition on the fruit pulp. Mango for export is subjected to hydrothermal treatment as a quarantine method for the control of this pest, but exposure to heat for long periods of time reduces considerably the quality and shelf-life of treated fruit. The aim of this work was to study morphological changes of third-instar larvae and adults of A. ludens after in vitro exposure to high temperature at sublethal times. A heating block system was used to expose larvae at 46.1°C for 19.6 and 12.9 min, producing 94.6 and 70% mortality, respectively. Treated larvae were processed for optical microscopy. A fraction of surviving treated larvae was separated into containers with artificial diet to allow development into adults. Adult sexual organs were dissected and processed for transmission electron microscopy analysis. Results showed that 94.6% of the treated larvae died at 46.1°C for 19.6 min and none of the surviving larvae eclosed to adulthood, as they developed as malformed puparia. For the in vitro treatment at 46.1°C during 12.9 min, 70% of the treated larvae died and only 3.75% reached the adult stage, but ultrastructural damage in the male testes and in the female ovaries was observed. Additionally, 11.1% of the adult flies from the in vitro treatment also showed wing malformation and were incapable of flying. The analysis showed that surviving flies were unable to reproduce.

Enhancement of nutritional properties, and antioxidant and antihypertensive potential of black common bean seeds by optimizing the solid state bioconversion process.

The aim of this work was to obtain a functional flour with enhanced nutritional properties, and antioxidant and antihypertensive potential from black bean seeds by optimizing the solid state bioconversion (SSB) process using a Rhizopus oligoporus strain. Response surface methodology was applied as optimization technique. A central composite experimental design with two factors [fermentation temperature (FT) = 30-40 °C/fermentation time (Ft) = 6-108 h] and five levels was used (13 treatments). The bioprocessed cotyledons from each treatment were dried, milled, and blended with its previously dried-milled seed coats. The best combination FT/Ft of SSB to obtain the functional flour was 38 °C/100 h. SSB increased the calculated protein efficiency ratio (from 1.59 to 2.40), antioxidant activity (from 13 948 to 22 733 µmol ET/100 g, dw), total phenolic compounds (TPC) (from 190 to 432 mg EGA/100 g, dw) and antihypertensive potential (IC(50) from 95.57 to 0.0321 µg/mL). SSB is an effective strategy to improve the TPC of common beans for enhanced functionality.

Valorisation of biodiesel production wastes: Anaerobic digestion of residual Tetraselmis suecica biomass and co-digestion with glycerol.

One of the principal opportunity areas in the development of the microalgal biodiesel industry is the energy recovery from the solid microalgal biomass residues to optimise the fuel production. This work reports the cumulative methane yields reached from the anaerobic digestion of the solid microalgal biomass residues using different types of inocula, reporting also the improvement of biogas production using the co-digestion of microalgal biomass with glycerol. Results demonstrate that the solid microalgal biomass residues showed better biogas production using a mesophilic inoculum, reaching almost two-fold higher methane production than under thermophilic conditions. Furthermore, the solid microalgal biomass residues methane production rate showed an increase from 173.78 ± 9.57 to 438.46 ± 40.50 mL of methane per gram of volatile solids, when the co-digestion with glycerol was performed. These results are crucial to improve the energy balance of the biodiesel production from Tetraselmis suecica, as well as proposing an alternative way to treat the wastes derived from the microalgae biodiesel production.

Solid-state bioconversion of chickpea (Cicer arietinum L.) by Rhizopus oligosporus to improve total phenolic content, antioxidant activity and hypoglycemic functionality.

The objective of this investigation was to study the effect of time during solid state bioconversion (SSB) on total phenolic content (TPC), antioxidant activity (AoxA), and inhibitory properties against α-amylase and α-glucosidase of chickpea. Chickpea cotyledons were inoculated with a suspension of Rhizopus oligosporus and incubated at 35 °C for 24, 36, 48, 60, 72, 84, 96 and 108 h. The best time to produce bioprocessed chickpea (added with seed coats) flour with the highest AoxA was 108 h. SSB substantially increased TPC and AoxA of chickpea extracts in 2.78 and 1.80-1.94 times, respectively. At 36 and 96 h of fermentation, the SSB process improved in vitro α-amylase and α-glucosidase inhibition (AI and GI indexes) activities of chickpea extracts in 83 and 370%, respectively. SSB is a good strategy to enhance health-linked functionality of chickpea, due to improved TPC, AoxA and content of strong natural inhibitors of enzymes associated with diabetes.

Increasing the antioxidant activity, total phenolic and flavonoid contents by optimizing the germination conditions of amaranth seeds.

The aim of this study was to optimize the germination conditions of amaranth seeds that would maximize the antioxidant activity (AoxA), total phenolic (TPC), and flavonoid (TFC) contents. To optimize the germination bioprocess, response surface methodology was applied over three response variables (AoxA, TPC, TFC). A central composite rotable experimental design with two factors [germination temperature (GT), 20-45 ºC; germination time (Gt), 14-120 h] in five levels was used; 13 treatments were generated. The amaranth seeds were soaked in distilled water (25 °C/6 h) before germination. The sprouts from each treatment were dried (50 °C/8 h), cooled, and ground to obtain germinated amaranth flours (GAF). The best combination of germination bioprocess variables for producing optimized GAF with the highest AoxA [21.56 mmol trolox equivalent (TE)/100 g sample, dw], TPC [247.63 mg gallic acid equivalent (GAE)/100 g sample, dw], and TFC [81.39 mg catechin equivalent (CAE)/100 g sample, dw] was GT = 30 ºC/Gt = 78 h. The germination bioprocess increased AoxA, TPC, and TFC in 300-470, 829, and 213%, respectively. The germination is an effective strategy to increase the TPC and TFC of amaranth seeds for enhancing functionality with improved antioxidant activity.

Fully Automated Flow Protocol for C(sp3)-C(sp3) Bond Formation from Tertiary Amides and Alkyl Halides.

Herein, we present a novel C(sp3)-C(sp3) bond-forming protocol via the reductive coupling of abundant tertiary amides with organozinc reagents prepared in situ from their corresponding alkyl halides. Using a multistep fully automated flow protocol, this reaction could be used for both library synthesis and target molecule synthesis on the gram-scale starting from bench-stable reagents. Additionally, excellent chemoselectivity and functional group tolerance make it ideal for late-stage diversification of druglike molecules.

An aspartate residue in the external vestibule of GLYT2 (glycine transporter 2) controls cation access and transport coupling.

Synaptic glycine levels are controlled by GLYTs (glycine transporters). GLYT1 is the main regulator of synaptic glycine concentrations and catalyses Na+-Cl--glycine co-transport with a 2:1:1 stoichiometry. In contrast, neuronal GLYT2 supplies glycine to the presynaptic terminal with a 3:1:1 stoichiometry. We subjected homology models of GLYT1 and GLYT2 to molecular dynamics simulations in the presence of Na+. Using molecular interaction potential maps and in silico mutagenesis, we identified a conserved region in the GLYT2 external vestibule likely to be involved in Na+ interactions. Replacement of Asp471 in this region reduced Na+ affinity and Na+ co-operativity of transport, an effect not produced in the homologous position (Asp295) in GLYT1. Unlike the GLYT1-Asp295 mutation, this Asp471 mutant increased sodium leakage and non-stoichiometric uncoupled ion movements through GLYT2, as determined by simultaneously measuring current and [3H]glycine accumulation. The homologous Asp471 and Asp295 positions exhibited distinct cation-sensitive external accessibility, and they were involved in Na+ and Li+-induced conformational changes. Although these two cations had opposite effects on GLYT1, they had comparable effects on accessibility in GLYT2, explaining the inhibitory and stimulatory responses to lithium exhibited by the two transporters. On the basis of these findings, we propose a role for Asp471 in controlling cation access to GLYT2 Na+ sites, ion coupling during transport and the subsequent conformational changes.

The effect of social determinants of health on utilization of surgical treatment for hepatocellular carcinoma patients.

BACKGROUND: A paucity of data exists on how social determinants of health (SDOH) influence treatment for Hepatocellular carcinoma (HCC). We investigated associations between SDOH (healthcare access, education, social/community context, economic stability, and built/neighborhood environment) and receipt of surgery. METHODS: The Pennsylvania Liver Cancer Registry was linked with neighborhood SDOH from the American Community Survey. Multilevel logistic regression models with patient and neighborhood SDOH variables were developed. RESULTS: Of 9423 HCC patients, 2393 were stage I. Only 36.3% of stage I patients received surgery. Black patients had significantly lower odds of surgery vs Whites (OR = 0.73; p < 0.01), but not after adjustments for SDOH. All 5 SDOH domains were associated with odds of surgery overall; 2 domains were associated in Stage I patients, social context (e.g., racial concentration, p = 0.03) and insurance access (p < 0.01). CONCLUSIONS: SDOH impact utilization of surgery for HCC. Findings can guide healthcare professionals to create programs for populations at risk for poor liver cancer outcomes.

High-Efficiency Removal of Lead and Nickel Using Four Inert Dry Biomasses: Insights into the Adsorption Mechanisms.

In this study, inert dry bioadsorbents prepared from corn cob residues (CCR), cocoa husk (CH), plantain peels (PP), and cassava peels (CP) were used as adsorbents of heavy metal ions (Pb2+ and Ni2+) in single-batch adsorption experiments from synthetic aqueous solutions. The physicochemical properties of the bioadsorbents and the adsorption mechanisms were evaluated using different experimental techniques. The results showed that electrostatic attraction, cation exchange, and surface complexation were the main mechanisms involved in the adsorption of metals onto the evaluated bioadsorbents. The percentage removal of Pb2+ and Ni2+ increased with higher adsorbent dosage, with Pb2+ exhibiting greater biosorption capacity than Ni2+. The bioadsorbents showed promising potential for adsorbing Pb2+ with monolayer adsorption capacities of 699.267, 568.794, 101.535, and 116.820 mg/g when using PP, CCR, CH, and CP, respectively. For Ni2+, Langmuir's parameter had values of 10.402, 26.984, 18.883, and 21.615, respectively, for PP, CCR, CH, and CP. Kinetics data fitted by the pseudo-second-order model revealed that the adsorption rate follows this order: CH > CP > CCR > PP for Pb2+, and CH > CCR > PP > CP for Ni2+. The adsorption mechanism was found to be controlled by ion exchange and precipitation. These findings suggest that the dry raw biomasses of corn cob residues, cocoa husk, cassava, and plantain peels can effectively remove lead and nickel, but further research is needed to explore their application in industrial-scale and continuous systems.

DFT studies on cobalt-catalyzed cyclotrimerization reactions: the mechanism and origin of reaction improvement under microwave irradiation.

A DFT computational mechanistic study of the [2+2+2] cyclotrimerization of a diyne with benzonitrile, catalyzed by a cobalt complex, has been carried out. Three alternative catalytic cycles have been examined together with the precatalytic step (responsible for the induction period). The favored mechanism takes place by means of an intramolecular metal-assisted [4+2] cycloaddition. The beneficial role of microwave activation has been studied. It is concluded that microwave irradiation can decrease the catalytic induction period through thermal effects and can also increase the triplet lifetime and promote the reaction, thus improving the final yield.