Dynamics of Water Intrusion in Polyelectrolyte-Bound Kaolinite: An Insight into Durability Mechanisms via Atomistic Modeling.

This research addresses interaction mechanisms of water-soluble polymers used as soil mineral stabilizers via atomistic classical molecular dynamics (MD). Specifically, this study addresses polyelectrolyte interactions with kaolinite, a ubiquitous clay mineral, in soils. The two water-soluble polymeric species evaluated are PSS: poly(4-sodium styrenesulfonate) and PDADMAC: poly(diallyldimethylammonium chloride). The primary focus is the evaluation of water migration through a polymer-kaolinite composite system, the resulting molecular arrangement and interactions, and the extents of water migration through the polymeric phase-binding kaolinite interfacial planes. Mean square displacement (MSD) analysis was used to quantify the motion of the system species from the MD trajectories by calculation of self-diffusion coefficients and comparison of the curves obtained. The MD results indicate that water infiltrates the polyelectrolyte phase adhering to the mineral interfaces. Nevertheless, the MSD analysis results indicate a 55.8% reduction in water self-diffusion with respect to pure mineral-confined water. This is a compelling indication that polyelectrolytes can hinder water movement. Most importantly, MSD analysis of both polyelectrolyte species shows that the movement of the chains is negligible relative to that of water. These results strongly suggest that the movement of polymer phases is restricted only to local chain mobility and a rather bound state to the mineral surfaces prevails.

Open to interpretation: An integrated primary care behavioral health training approach for treating linguistically diverse patients.

INTRODUCTION: Integrated primary care settings serve an increasingly high volume of linguistically diverse patients. In English language-dominant countries, limited English proficiency (LEP) is associated with disparities in access and quality of behavioral health (BH) care. Interpretive services (IS) aim to address these disparities by assisting in the delivery of clinical care between patients and providers who speak different languages. Yet, there is a need for greater emphasis on the utilization of IS in clinical training for BH professionals (e.g., psychology, social work, counseling, and family therapy). METHOD: In this conceptual article, we describe a BH practicum rotation for predoctoral psychology trainees in a free, student-run integrated primary care clinic that largely serves uninsured adults with LEP. First, we discuss our training model which includes a 90-min didactic lecture on IS for BH and supervised applied clinical experiences (e.g., psychotherapy, warm handoffs, and consultation). Then, we present vignettes prepared by trainees about the challenges and benefits associated with delivering BH care with IS at the predoctoral level of training. RESULTS: From the practicum experience, clinical psychology trainees reported improved knowledge and competencies in utilizing IS as well as generalizable skills for delivering BH care with a focus on multicultural practice. DISCUSSION: We recommend that other integrated primary care BH training sites consider emphasizing training in IS. This article concludes with recommendations for implementation and dissemination of our training model on other sites. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A Cooperative DNA Catalyst.

DNA catalysts are fundamental building blocks for diverse molecular information-processing circuits. Allosteric control of DNA catalysts has been developed to activate desired catalytic pathways at desired times. Here we introduce a new type of DNA catalyst that we call a cooperative catalyst: a pair of reversible reactions are employed to drive a catalytic cycle in which two signal species, which can be interpreted as an activator and an input, both exhibit catalytic behavior for output production. We demonstrate the role of a dissociation toehold in controlling the kinetics of the reaction pathway and the significance of a wobble base pair in promoting the robustness of the activator. We show near-complete output production with input and activator concentrations that are 0.1 times the gate concentration. The system involves just a double-stranded gate species and a single-stranded fuel species, as simple as the seesaw DNA catalyst, which has no allosteric control. The simplicity and modularity of the design make the cooperative DNA catalyst an exciting addition to strand-displacement motifs for general-purpose computation and dynamics.

Quantum Chemical Modeling of the Effects of Hydrated Lime (Calcium Hydroxide) as a Filler in Bituminous Materials.

Hydrated lime is widely used as a mineral filler to improve several properties of bituminous materials such as reducing the susceptibility of the composite to moisture-induced damage. Although experimental evidence supports the efficacy of using hydrated lime as a mineral filler, the molecular scale mechanism of reactivity of hydrated lime within the bitumen to reduce moisture damage is not understood. This is important when considering the durability of structural applications of bituminous materials such as asphalt concrete pavements subjected to both environmental and loading extremes. In this study, the interaction between hydrated lime and the key molecular building blocks of bitumen is modeled using density functional theory and compared against analogues of other common fillers such as calcite and quartz. Free energies of dissociation (ΔG dissoc) are calculated, and the nature of the bonds is characterized with contour maps of the Laplacian of the electron density. Hydrated lime is capable of reacting with specific functional groups in bitumen moieties and developing strong, water-resistant complexes. Among the functional groups investigated, carboxylic acids are the preferential reaction sites between hydrated lime and the bitumen moieties. Values as high as ΔG dissoc = +49.42 kcal/mol are reported for hydrated lime with water as the surrounding solvent. In contrast, analogues of calcite (ΔG dissoc = +15.84 kcal/mol) and quartz (ΔG dissoc = +4.76 kcal/mol) are unable to chemically react as strongly as hydrated lime in the presence of water. Contour maps of the Laplacian of the electron density indicate that the bonds between hydrated lime and model asphalt moieties are of an ionic nature. The atomistic modeling results correlate with thermodynamic calculations derived from experimental constants and are consistent with infrared spectrometric data.

Analytical tests to evaluate pozzolanic reaction in lime stabilized soils.

Shrink-swell soils are predominant in various parts of the parts of the world. Lime has been extensively used to reduce the shrink-swell mechanism as it chemically reacts with soil minerals forming pozzolanic products such as calcite and calcium-silicate-hydrate (C-S-H). Conventionally, whether chemical treatment of soils results in effective pozzolanic stabilization reactions is determined anecdotally through engineering tests including unconfined compressive strength, plasticity index (PI), and pH tests. This study builds on existing literature regarding how more direct quantification of pozzolanic products can be obtained through tests that directly identify and quantify pozzolanic products, specifically in lime-treated clay soils. Specifically, x-ray diffraction (XRD) and differential thermogravimetric analysis (DTA) are used for this testing. Expansive soils with plasticity indices above 25% were selected for this study. Engineering tests on these lime-treated soils indicated significant improvement in strength and reduction in PI. In XRD analysis, pozzolanic products are assessed by the location and intensity of x-ray peak(s). The XRD data show a decrease in the intensity of alumio-silicate minerals such as kaolinite and smectite; silica and alumina are dissolved at a high pH and converted to pozzolanic products such as calcium-silicate-hydrate (C-S-H). DTA indicates the presence of C-S-H with the characteristic weight loss from 140°C to 250°C.The methodology describes the following: ● Sample preparation steps for XRD and DTA analysis. ● Analysis of XRD results and DTA analysis.

Correction: Therapeutic targeting of Id2 reduces growth of human colorectal carcinoma in the murine liver.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

No longer any role for routine follow-up chest x-rays in men with stage I germ cell cancer.

Following radical orchidectomy for testicular cancer, most patients undergo protocolled surveillance to detect tumour recurrences rather than receive adjuvant chemotherapy. Current United Kingdom national and most international guidelines recommend that patients require a chest x-ray (CXR) and serum tumour markers at each follow-up visit as well as regular CT scans; there is however, variation among cancer centres with follow-up protocols. Seminomas often do not cause tumour marker elevation; therefore, CT scans are the main diagnostic tool for detecting relapse. For non-seminomatous tumours, serum beta-HCG (HCG) and AFP levels are a very sensitive harbinger of relapse, but this only occurs in 50% of patients [1], and therefore, imaging remains as important. CXRs are meant to aid in the detection of lung recurrences and before the introduction of modern cross-sectional imaging in the early 1980s, CXRs would have been the only method of identifying lung metastasis. We examined the Thames Valley and Mount Vernon Cancer Centre databases to evaluate the role of CXRs in the 21st century for the follow-up of men with stage I testicular cancer between 2003 and 2015 to assess its value in diagnosing relapsed germ cell tumours. From a total of 1447 patients, we identified 159 relapses. All relapses were detected either by rising tumour markers or planned follow-up CT scans. Not a single relapse was identified on CXR. We conclude that with timely and appropriate modern cross-sectional imaging and tumour marker assays, the CXR no longer has any value in the routine surveillance of stage I testicular cancer and should be removed from follow-up guidelines and clinical practice. Omitting routine CXR from follow-up schedules will reduce anxiety as well as time that patients spend at hospitals and result in significant cost savings.

TRIF-dependent innate immune activation is critical for survival to neonatal gram-negative sepsis.

Current evidence suggests that neonatal immunity is functionally distinct from adults. Although TLR signaling through the adaptor protein, MyD88, has been shown to be critical for survival to sepsis in adults, little is known about the role of MyD88 or TRIF in neonatal sepsis. We demonstrate that TRIF(-/-) but not MyD88(-/-) neonates are highly susceptible to Escherichia coli peritonitis and bacteremia. This was associated with decreased innate immune recruitment and function. Importantly, we found that the reverse was true in adults that MyD88(-/-) but not TRIF(-/-) or wild-type adults are susceptible to E. coli peritonitis and bacteremia. In addition, we demonstrate that TRIF but not MyD88 signaling is critical for the TLR4 protective adjuvant effect we have previously demonstrated. These data suggest a differential requirement for the survival of neonates versus adults to Gram-negative infection, and that modulation of TRIF in neonates can be used to augment survival to neonatal sepsis.

Novel role for tumor-induced expansion of myeloid-derived cells in cancer cachexia.

Cancer progression is associated with inflammation, increased metabolic demand, infection, cachexia, and eventually death. Myeloid-derived suppressor cells (MDSCs) commonly expand during cancer and are associated with adaptive immune suppression and inflammatory metabolite production. We propose that cancer-induced cachexia is driven at least in part by the expansion of MDSCs. MDSC expansion in 4T1 mammary carcinoma-bearing hosts is associated with induction of a hepatic acute-phase protein response and altered host energy and fat metabolism, and eventually reduced survival to polymicrobial sepsis and endotoxemia. Similar results are also seen in mice bearing a Lewis lung carcinoma and a C26 colon adenocarcinoma. However, a similar cachexia response is not seen with equivalent growth of the 66C4 subclone of 4T1, in which MDSC expansion does not occur. Importantly, reducing MDSC numbers in 4T1-bearing animals can ameliorate some of these late responses and reduce susceptibility to inflammation-induced organ injury and death. In addition, administering MDSCs from both tumor- and nontumor-bearing mice can produce an acute-phase response. Thus, we propose a previously undescribed mechanism for the development of cancer cachexia, whereby progressive MDSC expansion contributes to changes in host protein and energy metabolism and reduced resistance to infection.

Chemoresistant colorectal cancer cells and cancer stem cells mediate growth and survival of bystander cells.

BACKGROUND: Recent studies suggest that cancer stem cells (CSCs) mediate chemoresistance, but interestingly, only a small percentage of cells in a resistant tumour are CSCs; this suggests that non-CSCs survive by other means. We hypothesised that chemoresistant colorectal cancer (CRC) cells generate soluble factors that enhance survival of chemonaive tumour cells. METHODS: Chemoresistant CRC cells were generated by serial passage in oxaliplatin (Ox cells). Conditioned media (CM) was collected from parental and oxaliplatin-resistant (OxR) cells. CRC cells were treated with CM and growth and survival were assessed. Tumour growth rates were determined in nude mice after cells were treated with CM. Mass spectrometry (MS) identified proteins in CM. Reverse phase protein microarray assays determined signalling effects of CM in parental cells. RESULTS: Oxaliplatin-resistant CM increased survival of chemo-naive cells. CSC CM also increased growth of parental cells. Parental and OxR mixed tumours grew larger than tumours composed of parental or OxR cells alone. Mass spectrometry detected unique survival-promoting factors in OxR CM compared with parental CM. Cells treated with OxR CM demonstrated early phosphorylation of EGFR and MEK1, with later upregulation of total Akt .We identified progranulin as a potential mediator of chemoresistance. CONCLUSION: Chemoresistant tumour cells and CSCs may promote resistance through soluble factors that mediate survival in otherwise chemosensitive tumour cells.

Chronic exposure of colorectal cancer cells to bevacizumab promotes compensatory pathways that mediate tumour cell migration.

BACKGROUND: Bevacizumab (Bev), a monoclonal antibody to vascular endothelial growth factor (VEGF), is used in combination with chemotherapy for the treatment of metastatic colorectal cancer (CRC). The effects of Bev on angiogenesis have been well described, but the direct effect of Bev on tumour cells is unknown. This study was carried out to determine the molecular and phenotypic changes in CRC cells after chronic Bev exposure in vitro. METHODS: Human CRC cell lines were chronically exposed (3 months) to Bev in vitro to develop Bev-adapted (Bev-A) cell lines. Vascular endothelial growth factor family members were determined by reverse transcription-polymerase chain reaction and western blotting. Migration and invasion was determined using standard in vitro assays. Intravenous injection of tumour cells was carried out to evaluate metastatic potential in mice. RESULTS: Bevacizumab-adapted cells were found to be more migratory and invasive than control cells (P<0.001). Bevacizumab-adapted cells showed higher levels of VEGF-A, -B, -C, placental growth factor (PlGF), VEGF receptor-1 (VEGFR-1) and phosphorylation of VEGFR-1. Furthermore, treatment with SU5416, a VEGFR protein tyrosine kinase inhibitor, led to significantly decreased cell migration in vitro (P<0.001). Bevacizumab-adapted cells were more metastatic in vivo (P<0.05). CONCLUSION: Chronic exposure of CRC cells to Bev (1) increased expression of VEGF-A, -B, -C, PlGF, VEGFR-1 and VEGFR-1 phosphorylation, (2) increased tumour cell migration and invasion, and (3) metastatic potential in vivo. Our study shows the functional significance of autocrine VEGF signalling in CRC cells.

Therapeutic targeting of Id2 reduces growth of human colorectal carcinoma in the murine liver.

During development inhibitor of DNA-bind-2 (Id2) regulates proliferation and differentiation. Id2 expression has been detected in cancer cells, yet its cellular function and validity as a therapeutic target remains largely unknown. Immunohistochemical analysis of colorectal cancer (CRC) specimens revealed that Id2 was undetectable in normal colonic mucosa, but occurs in 40% of primary tumors and in most CRC liver metastases (P<0.0001). Additionally, Id2 was expressed in all CRC cell lines assayed. CRC cells with reduced Id2 expression demonstrated reduced proliferation. Analysis of CRC cell cycle regulatory proteins showed that reducing Id2 levels reduces cyclin D1 levels and increased p21 levels. Reduction of Id2 expression also enhanced tumor cell apoptosis, increasing levels of the pro-apoptotic protein Bim/Bod, and cleavage of caspase-7 and poly (ADP-ribose) polymerase. In vivo studies show tumors derived from cells with decreased Id2 levels formed smaller tumors with fewer metastases compared with tumors with normal levels (P<0.05). Furthermore, intraperitoneal administration of Id2 small interfering RNA (siRNA) conjugated with the neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine decreased tumor burden in mice compared with control treatment (P=0.006). We conclude that Id2 is upregulated in CRC, and is important in promoting cell survival. In vivo targeting of Id2 by siRNA establishes that it is a valid therapeutic target where its expression occurs.

Multiple-return laser radar for three-dimensional imaging through obscurations.

A compact imaging laser radar was constructed and tested to investigate phenomenological issues in targeting, especially cases involving imaging through obscurations such as foliage and camouflage netting. The laser radar employs a Nd:YAG microchip laser that operates at a wavelength of 1.06 microm and produces pulses of 1.2-ns duration at a 3-kHz rate. The detector is a commercial indium gallium arsenide avalanche photodiode. A single computer controls the scanning mirrors and performs the digitization of the returning signal at 2 giga samples/s. A detailed description of the laser radar is presented as well as results from field experiments that examined its range accuracy capability and its ability to image a target through camouflage. Results of data collected from deciduous tree lines are also discussed to characterize the presence and quantity of multiple returns.

Extracapsular cataract extraction under local anaesthesia without retrobulbar injection.

Day-case cataract surgery and the need for local anaesthesia are likely to increase. Retrobulbar (and peribulbar) anaesthetic injection is a common technique in cataract surgery, but serious complications are persistently reported. Subconjunctival injection is an alternative that avoids these risks. This retrospective study compares two groups of patients that underwent extracapsular cataract surgery under local anaesthetic. One group (retrobulbar) had uncomplicated retrobulbar injection with bupivicaine and hyaluronidase. The other group (non-retrobulbar) had superior bulbar, subconjunctival infiltration with bupivicaine and hyaluronidase. The operative complications and postoperative visual outcomes were similar in both groups. These results may encourage the investigation and adoption of the subconjunctival alternative to retrobulbar anaesthetic injection in cataract surgery.

A comparative evaluation of timolol maleate and pilocarpine in the treatment of chronic open angle glaucoma.

Ninety-two eyes with newly-diagnosed chronic open angle glaucoma (COAG) were treated in a randomised prospective trial with either timolol or pilocarpine. Their visual field survival was monitored on a 3-monthly basis over 2 years using both Goldmann and Friedmann perimetry. Concomitant tonometric data was derived by applanation. Fields were assessed and quantified using algorithms designed to give the greatest sensitivity for glaucomatous field loss. Microcomputer programmes specifically designed for this purpose were used in the data collection and subsequent analysis.

Importance of visual field score and asymmetry in the detection of glaucoma.

The visual fields and intraocular pressures (IOP's) of 115 normal volunteers and 107 suspect/diagnosed early glaucoma subjects were recorded by Friedmann static perimetry and noncontact tonometry or applanation tonometry. The visual field data were analyzed statistically and quantified numerically by a microcomputer. The readings obtained from the suspect/diagnosed early glaucoma subjects were compared to those from an age-matched control group according to four criteria: highest field score; field score asymmetry; highest IOP; and IOP asymmetry. A combined field score and asymmetry analysis was found to be more sensitive, 86%, than a combined IOP and IOP asymmetry analysis, 56%. The combined field score and field score asymmetry analysis also gave a clear bimodal separation of subjects with early visual field defects from those with normal visual function.

Glaucoma assessment by microcomputer.

An automated system for comprehensively monitoring glaucoma patients is described. This economic and practical microcomputer data system has been designed to be thoroughly 'clinician oriented' through the collaborative efforts of ophthalmological and computer specialists. It incorporates novel and efficient methods for transferring both automated and manually recorded perimetry data into analysable digital form. The system is inexpensive, simple to use, maintains safe records, allows thorough analysis of patient data, and can considerably reduce the administrative load on ophthalmological clinics.

Visual field survival: the response to timolol therapy in open-angle glaucoma.

A simple method for quantifying visual field survival was devised to assess the progress of chronic simple glaucoma in 36 patients treated with timolol maleate over a 3-year period. Routine tonometric monitoring of the intraocular pressure (IOP) was carried out in conjunction with these Goldmann field studies. Statistical analysis revealed that field survival measurement provided a more consistent clinical guide to the progress of glaucoma under treatment than did IOP (p much less than 0.001). Timolol therapy was associated with sustained IOP reductions of 24.3-34.5%, and 63% of those treated who were monitored for field survival showed no significant field loss. The observed relationships of IOP to field survival are discussed.