Zeolites synthesis from phyllosilicates and their performance for CO2 adsorption.

Five phyllosilicates (kaolinite, montmorillonite, saponite, sepiolite and palygorskite) have been selected as starting materials for the synthesis of zeolites. Among them, kaolinite and montmorillonite display the lowest Si/Al molar ratio leading to aluminosilicates with high crystallinity. Thus, the hydrothermal treatment under basic conditions forms 4A zeolite when kaolinite is used as starting material while 13X zeolite is obtained when montmorillonite is used as starting material. The microporosity and CO2-adsorption capacity of the prepared zeolites are directly related to its crystallinity. Thus, in order to improve it, raw phyllosilicates were subjected to a microwave-assisted treatment to remove undesired Mg or Fe-species, which have a negative effect in the assembling of the zeolites by hydrothermal basic conditions in a second step. The highest adsorption value was 3.85 mmol/g at 25 °C and 760 mm of Hg for Mont-A-B sample after the consecutive treatments.

Small Molecule Antagonists of the DNA Repair ERCC1/XPA Protein-Protein Interaction.

The DNA excision repair protein ERCC1 and the DNA damage sensor protein, XPA are highly overexpressed in patient samples of cisplatin-resistant solid tumors including lung, bladder, ovarian, and testicular cancer. The repair of cisplatin-DNA crosslinks is dependent upon nucleotide excision repair (NER) that is modulated by protein-protein binding interactions of ERCC1, the endonuclease, XPF, and XPA. Thus, inhibition of their function is a potential therapeutic strategy for the selective sensitization of tumors to DNA-damaging platinum-based cancer therapy. Here, we report on new small-molecule antagonists of the ERCC1/XPA protein-protein interaction (PPI) discovered using a high-throughput competitive fluorescence polarization binding assay. We discovered a unique structural class of thiopyridine-3-carbonitrile PPI antagonists that block a truncated XPA polypeptide from binding to ERCC1. Preliminary hit-to-lead studies from compound 1 reveal structure-activity relationships (SAR) and identify lead compound 27 o with an EC50 of 4.7 µM. Furthermore, chemical shift perturbation mapping by NMR confirms that 1 binds within the same site as the truncated XPA67-80 peptide. These novel ERCC1 antagonists are useful chemical biology tools for investigating DNA damage repair pathways and provide a good starting point for medicinal chemistry optimization as therapeutics for sensitizing tumors to DNA damaging agents and overcoming resistance to platinum-based chemotherapy.

Use of computed tomography coronary calcium score for prediction of cardiovascular events in cancer patients: a retrospective cohort analysis.

BACKGROUND: CT- coronary calcium score, is one of the most studied and widely available modalities in cardiovascular medicine. Coronary artery calcium score (CACS) is an established predictor of coronary artery disease. The 'standard of care' diagnostic modality to measure CACS is ECG-gated Cardiac Multi-Detector Computed Tomography. There is convincing evidence of a strong association between CACS and major cardiovascular (CV) events in asymptomatic individuals. Cancer patients (C) may have a higher risk for CV disease than non-cancer patients (NC) related not only to cancer treatments but also to shared biological factors and pathways. Thus, identifying tools for early detection of CV disease in this population is of utmost importance. METHODS: A retrospective cohort analysis was performed with patients from Cleveland Clinic Florida and Ohio who had CACS from 2017 to 2021. Patients who had cancer diagnosis prior to CACS were matched to NC for age and sex. CV events after their index CACS events were compared between C and NC, and matched control and propensity analysis were conducted. RESULTS: Ten thousand seven hundred forty-two patients had CACS; 703 cancer patients had CACS and were eligible. Extensive CACS (> 400) were significantly higher in cancer, 94 (13.37%) vs non-cancer patients, 76 (10.83%), P = 0.011. Furthermore, after propensity matched analysis, CACS > 400 was 14.8% in C vs 9.6% in NC, P = < 0.05. CV events were similar in both cohorts (p = NS), despite less CV risk factors in cancer patients (P = < 0.05). For the combined moderate (101-400) & extensive (> 400) CACS, the prevalence of stroke and peripheral arterial disease, a marker of systemic atherosclerosis, was significantly higher in patients with cancer (P < 0.01). CONCLUSIONS: Despite having fewer CV risk factors in our study, similar CACS in cancer patients are suggestive of a higher prevalence of CV disease independent of traditional risk factors. High CACS and the overall prevalence of vascular events were more frequent in patients with cancer. Higher prevalence of peripheral arterial disease and cerebrovascular accident further suggests the increased atherosclerotic burden in C.

Effects of a cardiopulmonary telerehabilitation using functional exercises in individuals after COVID-19 hospital discharge: A randomized controlled trial.

INTRODUCTION: Individuals with severe coronavirus disease 2019 (COVID-19) may present respiratory and motor complications, requiring rehabilitation programs (RP) for long periods. However, access to cardiopulmonary rehabilitation is poor. Cardiopulmonary telerehabilitation is an alternative for cardiopulmonary dysfunction, improving functional capacity, dyspnea, and quality of life. Moreover, few clinical trials verified the effectiveness of telerehabilitation using functional exercise for post-COVID symptoms. Thus, the present study aimed to verify the effects of cardiopulmonary telerehabilitation using functional and accessible exercises in individuals after COVID-19 hospital discharge. METHODS: This blinded, randomized, and controlled clinical trial and included 67 adult individuals after COVID-19 hospital discharge. Participants were randomized into the groups of telerehabilitation (TG; n = 33) and control (CG; n = 34). TG underwent an individualized exercise program (functional and accessible exercises) supervised by a physical therapist (videoconference), and CG received guidance on general care and self-monitoring of vital signs (videoconference). The primary outcome was performance and physiological responses on the 6-minute step test (6MST). Secondary outcomes were performance on the 2-minute stationary walk test (2MSWT), 30-second chair stand test (30CST), and quality of life using the 36-Item Short Form Health Survey (SF-36) questionnaire physical functioning concept (PF). RESULTS: Functional capacity (6MST) improved by 28 ± 17 steps in TG and 15 ± 26 in CG (p = 0.04). For secondary outcomes, performance on 2MSWT increased by 39 ± 6 steps in TG and 10 ± 6 in CG (p = 0.00); 30CST by 3 ± 1 repetitions in TG and 1.5 ± 0.5 in CG (p = 0.05); and PF (SF-36) by 17 ± 4 points in TG and 12 ± 4 in CG (p = 0.00). Also, peak oxygen uptake VO2peak (6MST) improved by 3.8 ± 1 mL min-1 kg-1 in TG and 4.1 ± 1 in CG (p = 0.6), and heart rate demand (6MST) by 11 ± 37% in TG and -4 ± 19% in CG (p = 0.04). CONCLUSIONS: Cardiopulmonary telerehabilitation using functional exercises improved the exercise and functional capacity assessed using 6MST, 30CST, and 2MSWT and the quality of life of individuals after COVID-19 hospital discharge.

Health-Related Quality of Life and Daily Physical Activity Level in Patients with COPD- a Cluster Analysis.

Patients with chronic obstructive pulmonary disease (COPD) may have a limited level of physical activity in daily life (PADL) and health-related quality of life (HRQOL). The interrelationships of these variables should be measure by cluster analysis to characterize this population and enable rehabilitation programs to target each patient profile identified. This study investigates different phenotypes in COPD according to PADL and HRQOL. A cross-sectional study with cluster analysis was done, in which 76 people with COPD were submitted to measurements to characterize the sample on first day, followed by used of physical activity monitor, which was worn for 7 days. After 7 days, the six-minute walk test (6MWT) and HRQOL questionnaires were applied (St. George's Respiratory Questionnaire). The main results: three phenotypes were identified (A, B and C), with phenotype A who exhibited an inactive physical activity level and HRQOL scores above the value deemed satisfactory, phenotype B those with active physical activity level and poor HRQOL scores, and phenotype C subjects with inactive physical activity level and HRQOL scores but the value is close to cutoff point. To conclude, three phenotypes were found, with one indicating disproportionality between PADL and HRQOL.

Growing emergence of drug-resistant Pseudomonas aeruginosa and attenuation of its virulence using quorum sensing inhibitors: A critical review.

A perilous increase in the number of bacterial infections has led to developing throngs of antibiotics for increasing the quality and expectancy of life. Pseudomonas aeruginosa is becoming resistant to all known conventional antimicrobial agents thereby posing a deadly threat to the human population. Nowadays, targeting virulence traits of infectious agents is an alternative approach to antimicrobials that is gaining much popularity to fight antimicrobial resistance. Quorum sensing (QS) involves interspecies communication via a chemical signaling pathway. Under this mechanism, cells work in a concerted manner, communicate with each other with the help of signaling molecules called auto-inducers (AI). The virulence of these strains is driven by genes, whose expression is regulated by AI, which in turn acts as transcriptional activators. Moreover, the problem of antibiotic-resistance in case of infections caused by P. aeruginosa becomes more alarming among immune-compromised patients, where the infectious agents easily take over the cellular machinery of the host while hidden in the QS mediated biofilms. Inhibition of the QS circuit of P. aeruginosa by targeting various signaling pathways such as LasR, RhlR, Pqs, and QScR transcriptional proteins will help in blocking downstream signal transducers which could result in reducing the bacterial virulence. The anti-virulence agent does not pose an immediate selective pressure on growing bacterium and thus reduces the pathogenicity without harming the target species. Here, we review exclusively, the growing emergence of multi-drug resistant (MDR) P. aeruginosa and the critical literature survey of QS inhibitors with their potential application of blocking P. aeruginosa infections.

Electrochemical and quantum mechanical investigation of various small molecule organic compounds as corrosion inhibitors in mild steel.

The corrosion inhibition property of selected small organic compounds was investigated using electrochemical measurements, including potentiodynamic polarization (PDP), linear polarization resistance (LPR), electrochemical impedance spectroscopy (EIS), and density functional theory (DFT) calculations. The inhibition efficiency (IE %) of the inhibitor on mild steel (MS) in 1 M HCl was then determined. Results show that the presence of the inhibitors resulted in decreased corrosion current density (I corr) values and increased polarization resistance (R p). Furthermore, the use of higher concentrations of inhibitors led to an increased inhibition efficiency. Tafel slopes and shifts in the E corr values suggested that the inhibitors tested are mixed-type inhibitors that form a protective layer on the surface of the substrate. Of the organic compound inhibitors tested, the inhibitor 4-ethylpyridine (EP) exhibited the highest R p values and inhibition efficiency values from the PDP, LPR, and EIS analyses, respectively. DFT calculations showed negative adsorption energies and confirmed the chemisorption of the inhibitors allowing for the formation of a hydrophobic protective film against corrosion and correlations between the quantum chemical values and electrochemical data were demonstrated. The results show the influence of the presence of electronegative O, S, and N atoms, as well as the role of aromatic rings in the promotion of surface protection by preventing aggressive ionic species from binding onto MS.

Highly Sensitive and Selective Spiropyran-Based Sensor for Copper(II) Quantification.

The metal-binding capabilities of the spiropyran family of molecular switches have been explored for several purposes from sensing to optical circuits. Metal-selective sensing has been of great interest for applications ranging from environmental assays to industrial quality control, but sensitive metal detection for field-based assays has been elusive. In this work, we demonstrate colorimetric copper sensing at low micromolar levels. Dimethylamine-functionalized spiropyran (SP1) was synthesized and its metal-sensing properties were investigated using UV-vis spectrophotometry. The formation of a metal complex between SP1 and Cu2+ was associated with a color change that can be observed by the naked eye as low as ≈6 µM and the limit of detection was found to be 0.11 µM via UV-vis spectrometry. Colorimetric data showed linearity of response in a physiologically relevant range (0-20 µM Cu2+) with high selectivity for Cu2+ ions over biologically and environmentally relevant metals such as Na+, K+, Mn2+, Ca2+, Zn2+, Co2+, Mg2+, Ni2+, Fe3+, Cd2+, and Pb2+. Since the color change accompanying SP1-Cu2+ complex formation could be detected at low micromolar concentrations, SP1 could be viable for field testing of trace Cu2+ ions.

Complex formation of silver(I) ions with a glucosinolate derivative: structural and mechanistic insights into myrosinase-mimicking C-S bond cleavage.

The crystal structure of an unprecedented silver complex of O-acetylsinigrin has shown chelating bonds of the sulfated thiohydroximate and an η2-bond of the ethylene moiety with Ag(i). Mechanistic studies on the formation and decomposition of the complex by the 1H NMR measurements and theoretical calculations with the DFT method indicated relevance to the glucosinolate degradation in biological systems.

A new species of emThamnodynastes/em Wagler, 1830 from western Amazonia, with notes on morphology for members of the emThamnodynastes/em empallidus/em group (Serpentes, Dipsadidae, Tachymenini).

The genus Thamnodynastes is the most diverse within the tribe Tachymenini, with an extensive and complex taxonomic history. The brief descriptions and lack of robust diagnostic characters are the main sources for identification errors and for the difficulty to assess the diversity estimates of the genus. The Thamnodynastes pallidus group was briefly designated to encompass the most arboreal species of the genus, with thinner bodies and longer tails: T. pallidus, T. longicaudus, T. sertanejo, and a fourth undescribed species. After its designation, no other paper addressed this group and its morphological variation, especially for the hemipenis, is still undetermined. After the analysis of all species of Thamnodynastes we were able to corroborate the distinctiveness of the T. pallidus group and to accurately diagnose its fourth species from the western portion of the Amazonia lowlands. The new species is distinguishable from all congeners, except T. sertanejo, by the absence of ventral longitudinal stripes, 17/17/11 dorsal scale rows, and dorsal dark brown blotches on the anterior third of the body. The new species is distinguished from T. sertanejo by the higher number of subcaudals, lower number of ventrals, and smaller body and head sizes. We also provide additional diagnostic features for the Thamnodynastes pallidus group, including new data on hemipenial variation. Finally, we briefly discuss the defensive behavior and morphological characters associated with arboreality in members of the T. pallidus species group.

Submucosal Tunneling Endoscopic Resection.

Minimally invasive endoscopic resection procedures continue to evolve, with submucosal tunneling endoscopic resection (STER) being a durable option for en bloc resection of submucosal tumors. Whether STER can be effectively used for larger (>3.5 cm) lesions remains to be seen. STER-ET is a novel approach for removal of extraluminal tumors, but data are currently limited to support its use.

Effect of Structure and Intramolecular Distances on Photoswitchable Magnetic Resonance Imaging Contrast Agents.

Light-activated sensors are of great interest for biological applications but are limited by the depth of penetration of light. We have been interested in transducing light activation to a magnetic signal that can be detected through noninvasive imaging by magnetic resonance imaging (MRI). We have previously developed agents incorporating spiropyran derivatives as the sensing moiety and characterized features that influence photoswitching; however, we found the MRI response to be unpredictable. In this work, we delve deeper into the potential mechanisms for the observed MRI responses in an effort to better understand the structural effects on controlling magnetic properties. A series of light-activatable MRI contrast agents were synthesized and characterized to assess the effect of spiropyran positioning on contrast agent functions and properties. These compounds are based on the same spiropyran skeleton, also named 1',3',3'-trimethyl-6-nitrospiro[chromene-2,2-indoline], which is linked with an MRI contrast agent, gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7-triacetate (DO3A). We investigated the photo-to-magnetic conversion properties of these novel compounds by adjusting linker lengths over a range from three to seven methylene groups. The primary results indicated that the contrast agent with a five-carbon linker (25) showed the highest light-sensing ability after irradiation with visible light. The results will aid in the design of future spiropyran-based MRI sensors.

Evaluation of Drosophila chromosomal segments proposed by means of simulations of possessing hybrid sterility genes from reproductive isolation.

In heterozygote state, we interogressed three chromosomal segments of Drosophila koepferae in D. buzzatii. The effect of each introgression was evaluated in the fertility of the segmental males, quantifying the amount of offspring produced. Through specific crosses method, we generated Drosophila segmental isolines carrying specific chromosomal introgression segments. The introgressions were monitored cytogenetically by the method of molecular markers of chromosomal asynapsis. The statistical analysis showed that none of the three segments evaluated, introgressed individually or in pairs, as well as cis or trans, do not produce sterility in the segmental males, as determined by the normal productions of offspring. Additional introgressions using other larger segments show that when the introgressions reach a minimum size of 31.15%, they produce sterility. It is concluded that the hybrid sterility genes present in the three segments evaluated did not act in strong epistasis, but show a pattern of gradual additive behaviour by requiring a minimum threshold size to produce sterility. Finally, we also isolated the smallest introgressing segment that has been reported for these species (2.19%), and for the first time we have managed to place it in homozygous state (data not shown), so we are now in the process of evaluating the ability to these segments in homozygous state.

Description of a second known Liotyphlops caissara specimen (Serpentes: Anomalepididae).

We recorded a second specimen of the poorly known insular blind snake Liotyphlops caissara. This new specimen expands the morphological variation of the number of dorsal scales in the genus Liotyphlops to 296 (vs. 304 in L. wilderi) and, considering the fact that the holotype of this species was destroyed, the present specimen represents the only available L. caissara individual in zoological collections. Also, this new record constitutes the first out of type locality and expands the distribution of the species in about 40 km to the northeastern. According to IUCN criteria (B1a, b [iii]), we suggest that L. caissara be included in the "Endangered" category, since it occurs in only two insular locations and exhibits an occurrence extension of <5,000 km² (about 355 km2).

DFT study on the effect of proximal residues on the Mycobacterium tuberculosis catalase-peroxidase (katG) heme compound I intermediate and its bonding interaction with isoniazid.

Isoniazid (INH) is converted into isonicotinyl radical through its interaction with the catalase-peroxidase (katG) enzyme present in the cells of Mycobacterium tuberculosis (M. tb.), the bacteria that causes the tuberculosis disease. This process is important because resistance of M. tb. cells to INH treatment has been associated with the failure of completion of this process. However, this process is poorly understood and there are a variety of conflicting theories about the details of the mechanism of this process. One theory suggests that INH binds to katG and transfers a single electron to the heme while the heme is in its two electron oxidized state, compound I [Fe(iv)Por˙+] (CpdI). In this study, DFT calculations at the UB3LYP/6-31g(d)-LANL2DZ level of theory are used to study the M. tb. katG CpdI molecule. Different models of the M. tb. CpdI molecule were prepared and the calculations revealed the impact of Trp321 on the electronic properties of the heme. Without Trp321 the heme assumed a triradical state with single electrons on the πxy and πyz orbitals of Fe and another on the a2u orbital of the porphyrin ring that can either be coupled with the first two, to assume a quartet state, or decoupled to form a doublet state. With Trp321, however, a transfer of an electron from the πTrp orbital to a2u porphyrin orbital leads to loss of radical character of the porphyrin and leaves the Trp321 group with a radical character. INH was observed to have strong interaction with CpdI and the absence of Trp321 significantly decreased the binding energy by 2 kcal mol-1 explaining the importance of Trp321 in the binding of INH. The results in this study show the importance of Trp321 in the binding of INH and its effect on its electronic properties, which is consistent with previous experimental findings that mutation of Trp321 results in an increase in drug resistance.

Detección y tipificación del Virus Papiloma Humano en el marco del tamizaje virológico para la detección de lesiones del cuello uterino en Asunción, Paraguay / Detection and typing of Human Papilloma Virus during a virological screening for detection of cervical lesions in Asunción, Paraguay

En Paraguay la incidencia de cáncer de cuello uterino (CCU) es superior a las observadas en otros países de la región. El agente etiológico asociado al CCU es el virus papiloma humano (VPH), esencialmente tipos de alto riesgo oncogénicos. El objetivo es describir aspectos epidemiológicos de la infección genital por el virus papiloma humano de alto riesgo (VPH-AR) en mujeres de 25 a 64 años que consultaron en servicios de Patología Cervical del MSPyBS, de mayo a diciembre de 2013. Se utilizó el Cobas 4800 HPV Test (Roche) que permite la detección individual de VPH-16 y VPH-18 y un pool de otros VPH-AR que incluye 12 genotipos de alto riesgo. Los otros VPH-AR fueron tipificados por hibridación reversa en línea (RLB). Entre las 495 mujeres incluidas, se detectaron 72 casos positivos (14,5%) de VPH-AR. Se identificaron 19 tipos virales; siendo el más frecuente VPH-16 (2,1%), seguido del VPH-31, 33, 58 y 66; el VPH-18 aparece en sexto lugar. Este trabajo aporta los primeros datos sobre la implementación de técnicas moleculares para detección y tipificación de VPH como parte del sistema de salud pública de Paraguay. El predominio de VPH-16, confirma su amplia circulación a nivel mundial y dado su mayor potencial oncogénico, representa una alerta a considerar, en especial en las mujeres mayores de 30 años portadoras de una infección persistente. Estos resultados apoyan la importancia de la implementación criteriosa y la utilización apropiada de las pruebas moleculares actualmente disponibles para la prevención y control del CCU(AU)

Annealing multicomponent supramolecular gels.

Annealing is widely used as a means of changing the physical properties of a material. The rate of heating and cooling used in the annealing process controls the final properties. Annealing can be used as a means of driving towards the, or at least a, thermodynamic minimum. There is surprisingly little information on annealing kinetically-trapped supramolecular gels. Here, we show that annealing multicomponent gels can be used to prepare materials with tunable mechanical properties. We show that annealing in a two-component gel leads to a self-sorted network, which has significantly different mechanical properties to the as-prepared gels. Whilst the fibres are self-sorted, we show that the annealing of this system leads to significant change in the network level of assembly, and it is this that leads to the increase in storage modulus. We also show that it is possible to selectively anneal only a single component in the mixture.

Theoretical insights on the binding of isoniazid to the active site residues of Mycobacterium tuberculosis catalase-peroxidase.

Isoniazid (INH) is known to cause the exclusive lethal action to Mycobacterium tuberculosis (M. tb.) cells because of the pathogen's own catalase-peroxidase (katG) enzyme that converts INH to a very reactive radical. Thus, in order to gain insights on the interaction of INH with the individual active site residues (Res) of katG, this study presents a computational approach via molecular docking and density functional theory (DFT) using augmented models to study the individual INH-Res interactions. Seven amino acid residues directly interacts with INH: Arg104, Asp137, His108, Ile228, Trp107, Tyr229, and Val230. The residues with the highest interaction energies are Arg104 (-39.64 kcal/mol) and Asp137 (-32.85 kcal/mol) mainly due to strong ion-dipole and H-bonding interactions present in the complexes, while the weakest interaction was observed for Ile228 (-13.78 kcal/mol). Molecular electrostatic potential surface revealed complementary regions for dipole interactions and charge distribution analysis further shows that INH generally donates electrons to the residues. The results in this study agrees with the previous experimental findings and provides new insights into the catalase dependent activation of INH and the methods presented may be valuable in the study of biological metabolism of molecules.

Grain zinc concentrations differ among Brazilian wheat genotypes and respond to zinc and nitrogen supply.

The combined application of nitrogen (N) and zinc (Zn) fertilizers is a promising agronomic strategy for the biofortification of wheat grain with Zn for human nutrition. A glasshouse experiment was carried out to assess the effects of supplying N on the uptake, translocation and accumulation of Zn in tissues of two wheat genotypes (Quartzo and BRS Parrudo) with contrasting potential for grain Zn biofortification. Winter wheat genotypes were grown to maturity in 5 cm diameter, 100 cm length tubes filled with a mixture of sand, grit and gravel (40:40:20 v/v/v) over a layer of 0.1 m3 of gravel, and supplied a full nutrient solution with low Zn (0.15 µM) or high Zn (2.25 µM) and low N (0.4 mM) or high N (4.0 mM) concentrations. High N supply increased biomass production, Zn concentration and Zn content of straw and grain in both Quartzo and BRS Parrudo. Grain Zn content more than doubled when the supplies of Zn and N were both increased from low to high in both genotypes. Quartzo had a greater grain yield than BRS Parrudo. BRS Parrudo had greater grain Zn concentration and Zn content than Quartzo. A greater N supply promoted better uptake, translocation to the shoot and accumulation of Zn within the grain. Quartzo and BRS Parrudo differed in their partitioning of biomass and Zn between tissues. It might be possible to combine the greater grain yield of Quartzo with the greater grain Zn accumulation of BRS Parrudo to deliver a greatly improved genotype for human food security.