Parents Perceptions: When an Adolescent Has Been Given a Dual Diagnosis of Chemical Dependency Coupled with Mental Illness

An overview of existing research shows that dually diagnosed individuals present a unique and complex challenge for family members and the professionals who work with them. This exploratory study examined the impact on and family perceptions of the dual disorders as well as their treatment experience. Face to face interviews were conducted with ten parents who were selected from a treatment facility on the basis of specific criteria mainly, parents of a dually diagnosed adolescent recently having been or currently in treatment. Selections were also based on availability and willingness to participate. Grounded theory techniques were used to analyze the data. Three themes emerged from the data: 1) coming to terms with illness, 2) issues for future of adolescents, and 3) perceptions of treatment experience. The findings of this research provide information for social workers working with dual diagnoses. In addition, the findings of this research will provide background information for future research on parents\u27 perceptions of dual diagnosis. It is hoped that the findings from this study will assist not only professionals, but also family and friends of the dually diagnosed individual

Growing and Handling of Bacterial Cultures within a Shared Core Facility for Integrated Structural Biology Program

We have established and optimized standard operating procedures for growing and handling bacterial cultures in a shared core laboratory to support Integrative Structural Biology. The Integrative Structural Biology effort within the Biomolecular Research Center allows researchers to generate new knowledge about protein and RNA structure and function. We aim to understand how biomolecules assemble into stable structures and how structural dynamics impacts their function. Here we describe specific procedures for growing and handling bacterial cultures for overexpression and isolation of recombinant proteins, 15N/13C uniform labeling of recombinant proteins, protein isolation and purification, and analysis of protein solubility that are ideal for implementation in a shared research core laboratory that serves a multitude of diverse customers and research laboratories

Modeling and Design of Polythiophene Gate Electrode ChemFETs for Environmental Pollutant Sensing

Water-borne pollutants such as volatile organic compounds are a serious environmental concern, which has increased the demand for chemical sensing elements. Solidstate sensors based on catalytic gate devices are a subject of current research, however they are restricted in practical applications because of their inability to operate at room temperature. Conducting polymer FETs, which employ a conducting gate polymer, have received much attention due to their unique electronic and optical properties. Polythiophene is chosen as the semi-conductive gate polymer in this work. A functional group attached to the polythiophene is used to detect analytes (i.e., mercury in this work) of interest. The selectivity of the derivitized polythiophene to mercury can he rationalized based on the size of the ring, presence of oxygen and nitrogen donor atoms. In this paper, the modeling and design of a polythiophene gate electrode ChemFET will he discussed. Specifically the model development and resultant device simulations using Silvaco TCAD will be presented. Using this model various current-voltage characteristics of the ChemFET corresponding to parameters such as substrate doping, gate oxide thickness, various gate stacks, and device geometries are presented

A Pipeline to Determine RT-QPCR Control Genes for Evolutionary Studies: Application to Primate Gene Expression across Multiple Tissues

Because many species-specific phenotypic differences are assumed to be caused by differential regulation of gene expression, many recent investigations have focused on measuring transcript abundance. Despite the availability of high-throughput platforms, quantitative real-time polymerase chain reaction (RT-QPCR) is often the method of choice because of its low cost and wider dynamic range. However, the accuracy of this technique heavily relies on the use of multiple valid control genes for normalization. We created a pipeline for choosing genes potentially useful as RT-QPCR control genes for measuring expression between human and chimpanzee samples across multiple tissues, using published microarrays and a measure of tissue-specificity. We identified 13 genes from the pipeline and from commonly used control genes: ACTB, USP49, ARGHGEF2, GSK3A, TBP, SDHA, EIF2B2, GPDH, YWHAZ, HPTR1, RPL13A, HMBS, and EEF2. We then tested these candidate genes and validated their expression stability across species. We established the rank order of the most preferable set of genes for single and combined tissues. Our results suggest that for at least three tissues (cerebral cortex, liver, and skeletal muscle), EIF2B2, EEF2, HMBS, and SDHA are useful genes for normalizing human and chimpanzee expression using RT-QPCR. Interestingly, other commonly used control genes, including TBP, GAPDH, and, especially ACTB do not perform as well. This pipeline could be easily adapted to other species for which expression data exist, providing taxonomically appropriate control genes for comparisons of gene expression among species

The new IOC and IAAF policies on female eligibility: old Emperor, new clothes?

The Caster Semenya debacle touched off by the 2009 Berlin World Athletics Championships resulted finally in IOC and IAAF abandonment of sex testing, which gave way to procedures that make female competition eligibility dependent upon the level of serum testosterone, which must be below the male range or instrumentally countered by androgen resistance. We argue that the new policy is unsustainable because (i) the testosterone-performance connection it posits is uncompelling; (ii) testosterone-induced female advantage is not ipso facto unfair advantage; (iii) the new policy reflects the gender policing impulses endemic to sport as well as the broader cultural impulses to monstrify women and to doctor women who have nothing wrong with them; (iv) female–male performance disparities are not the only reason for sex-segregated sport, but co-exist with respectable cultural and practical reasons, which (v) provide a powerful case for allowing athletes to compete in the sex category congruent with their gender identity

Expression and Purification of a Cleavable Recombinant Fortilin from \u3ci\u3eEscherichia coli\u3c/i\u3e for Structure Activity Studies

Complications related to atherosclerosis account for approximately 1 in 4 deaths in the United States and treatment has focused on lowering serum LDL-cholesterol levels with statins. However, approximately 50% of those diagnosed with atherosclerosis have blood cholesterol levels within normal parameters. Human fortilin is an anti-apoptotic protein and a factor in macrophage-mediated atherosclerosis and is hypothesized to protect inflammatory macrophages from apoptosis, leading to subsequent cardiac pathogenesis. Fortilin is unique because it provides a novel drug target for atherosclerosis that goes beyond lowering cholesterol and utilization of a solution nuclear magnetic resonance (NMR) spectroscopy, structure-based drug discovery approach requires milligram quantities of pure, bioactive, recombinant fortilin. Here, we designed expression constructs with different affinity tags and protease cleavage sites to find optimal conditions to obtain the quantity and purity of protein necessary for structure activity relationship studies. Plasmids encoding fortilin with maltose binding protein (MBP), 6-histidine (6His) and glutathione-S-transferase (GST), N- terminal affinity tags were expressed and purified from Escherichia coli (E. coli). Cleavage sites with tobacco etch virus (TEV) protease and human rhinovirus (HRV) 3C protease were assessed. Despite high levels of expression of soluble protein, the fusion constructs were resistant to proteinases without the inclusion of amino acids between the cleavage site and N-terminus. We surveyed constructs with increasing lengths of glycine/serine (GGS) linkers between the cleavage site and fortilin and found that inclusion of at least one GGS insert led to successful protease cleavage and pure fortilin with conserved binding to calcium as measured by NMR

Group versus individual academic detailing to improve the use of antihypertensive medications in primary care: a cluster-randomized controlled trial

Purpose To compare group versus individual academic detailing to increase diuretic or β-blocker use in hypertension. Methods We conducted a cluster-randomized controlled trial in a large health maintenance organization. Subjects (N=9820) were patients with newly treated hypertension in the year preceding the intervention (N=3692), the 9 months following the intervention (N=3556), and the second year following intervention (N=2572). We randomly allocated 3 practice sites to group detailing (N=227 prescribers), 3 to individual detailing (N=235 prescribers), and 3 to usual care (N=319 prescribers). Individual detailing entailed a physician-educator meeting individually with clinicians to address barriers to prescribing guideline-recommended medications. The group detailing intervention incorporated the same social marketing principles in small groups of clinicians. Results In the first year following the intervention, the rates of diuretic or β-blocker use increased by 13.2% in the group detailing practices, 12.5% in the individual detailing practices, and 6.2% in the usual care practices. As compared with usual care practices, diuretic or β-blocker use was more likely in group detailing practices (adjusted odds ratio (OR), 1.40; 95% confidence interval (CI), 1.11 – 1.76) and individual detailing practices (adjusted OR, 1.30; 95% CI, 0.95 – 1.79). Neither intervention affected blood pressure control. Two years following this single-visit intervention, there was still a trend suggesting a persistent effect of individual (OR, 1.22; 95% CI, 0.92 – 1.62), but not group, detailing (OR, 1.06; 95% CI, 0.80 – 1.39), as compared with usual care. Conclusion Both group and individual academic detailing improved antihypertensive prescribing over and above usual care but may require reinforcement to sustain improvements

Bioactive Recombinant Human Oncostatin M for NMR-Based Screening in Drug Discovery

Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure unlabeled and isotope enriched OSM from E. coli for biochemical and NMR studies. High yields (ca. 10 mg/L culture) were obtained in rich and minimal defined media cultures. Purified OSM was characterized by mass spectrometry and circular dichroism. The bioactivity was confirmed by induction of OSM/OSM receptor signaling through STAT3 phosphorylation in human breast cancer cells. Optimized buffer conditions yielded 1H, 15N HSQC NMR spectra with intense, well-dispersed peaks. Titration of 15N OSM with a small molecule inhibitor showed chemical shift perturbations for several key residues with a binding affinity of 12.2 ± 3.9 μM. These results demonstrate the value of bioactive recombinant human OSM for NMR-based small molecule screening

Sensitivity and specificity of the ECAS in Parkinson’s disease and Progressive Supranuclear Palsy

Disentangling Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) may be a diagnostic challenge. Cognitive signs may be useful, but existing screens are often insufficiently sensitive or unsuitable for assessing people with motor disorders. We investigated whether the newly developed ECAS, designed to be used with people with even severe motor disability, was sensitive to the cognitive impairment seen in PD and PSP and able to distinguish between these two disorders. Thirty patients with PD, 11 patients with PSP, and 40 healthy controls were assessed using the ECAS, as well as an extensive neuropsychological assessment. The ECAS detected cognitive impairment in 30% of the PD patients, all of whom fulfilled the diagnostic criteria for mild cognitive impairment. The ECAS was also able to detect cognitive impairment in PSP patients, with 81.8% of patients performing in the impaired range. The ECAS total score distinguished between the patients with PSP and healthy controls with high sensitivity (91.0) and specificity (86.8). Importantly, the ECAS was also able to distinguish between the two syndromes, with the measures of verbal fluency offering high sensitivity (82.0) and specificity (80.0). In sum, the ECAS is a quick, simple, and inexpensive test that can be used to support the differential diagnosis of PSP

Seminaphthofluorones are a family of water-soluble, low molecular weight, NIR-emitting fluorophores

A readily accessible new class of near infrared (NIR) molecular probes has been synthesized and evaluated. Specific fluorophores in this unique xanthene based regioisomeric seminaphthofluorone dye series exhibit a combination of desirable characteristics including (i) low molecular weight (339 amu), (ii) aqueous solubility, and (iii) dual excitation and emission from their fluorescent neutral and anionic forms. Importantly, systematic changes in the regiochemistry of benzannulation and the ionizable moieties afford (iv) tunable deep-red to NIR emission from anionic species and (v) enhanced Stokes shifts. Anionic SNAFR-6, exhibiting an unusually large Stokes shift of ≈200 nm (5,014 cm−1) in aqueous buffer, embodies an unprecedented fluorophore that emits NIR fluorescence when excited in the blue/green wavelength region. The successful use of SNAFR-6 in cellular imaging studies demonstrates proof-of-concept that this class of dyes possesses photophysical characteristics that allow their use in practical applications. Notably, each of the new fluorophores described is a minimal template structure for evaluation of their basic spectral properties, which may be further functionalized and optimized yielding concomitant improvements in their photophysical properties