Search

Neurochemical sensing with implantable devices has gained remarkable attention over the last few decades. A promising area of this research is the progress of novel electrodes as electrochemical tools for neurotransmitter detection in the brain. The boron-doped diamond (BDD) electrode is one such candidate that previously has been reported for its excellent electrochemical properties, including a wide working potential, superior chemical inertness and mechanical stability, good biocompatibility and resistance to fouling. Meanwhile, limited research has been conducted on the BDD as a microelectrode for neurochemical detection. Our team has developed a freestanding, all diamond microelectrode consisting of a boron-doped polycrystalline diamond core, encapsulated in an insulating polycrystalline diamond shell, with a cleaved planar tip for electrochemical sensing. This all-diamond electrode is advantageous due to its - (1) batch fabrication using wafer technology that eliminates traditional hand fabrication errors and inconsistencies, (2) absence of metal-based wires, or foundations, to improve biocompatibility and flexibility, and (3) sp 3 carbon surface with resistance to biofouling, i.e. adsorption of proteins or unwanted molecules at the electrode surface in a biological environment that impedes overall electrode performance. Here, we provide findings on further in vitro testing and development of the freestanding boron-doped diamond microelectrode (BDDME) for neurotransmitter detection using fast scan cyclic voltammetry (FSCV). In this report, we elaborate on - 1) an updated fabrication scheme and work flow to generate all diamond BDDMEs, 2) slow scan cyclic voltammetry measurements of reference and target analytes to understand basic electrochemical behavior of the electrode, and 3) FSCV characterization of common neurotransmitters, and overall favorability of serotonin (5-HT) detection. The BDDME showed a 2-fold increased FSCV response for 5-HT in comparison to dopamine (DA), with a limit of detection of 0.16 µM for 5-HT and 0.26 µM for DA. These results are intended to expand on the development of the next generation BDDME and guide future in vivo experiments, adding to the growing body of literature on implantable devices for neurochemical sensing.

The endangered population of humpback whales ( Megaptera novaeangliae ) breeding and calving off the Cape Verde Islands (CVI) are known to migrate to feeding areas located along the eastern margin of the North Atlantic Ocean (Iceland, and Norway). Here, we report for the first time a confirmed migration of an individual humpback whale from CVI breeding ground to a western North Atlantic feeding ground of West Greenland. This individual humpback, which was photographed and identified off the coast of West Greenland in 2021, was previously documented in CVI 22 years before (1999). An annual subsistence hunt for humpbacks occurs in West Greenland and the resighting at this location with a humpback whale from CVI has strong implications for the conservation efforts of the small CVI population., Competing Interests: The authors declare no competing interests., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Experimental and theoretical foundations for femtosecond time-resolved circular dichroism (TRCD) spectroscopy of excitonic systems are presented. In this method, the system is pumped with linearly polarized light and the signal is defined as the difference between the transient absorption spectrum probed with left and with right circularly polarized light. We present a new experimental setup with a polarization grating as key element to generate circularly polarized pulses. Herein the positive (negative) first order of the diffracted light is left-(right-)circularly polarized and serves as a probe pulse in a TRCD experiment. The grating is capable of transferring ultrashort broadband pulses ranging from 470 nm to 720 nm into two separate beams with opposite ellipticity. By applying a specific chopping scheme we can switch between left and right circular polarizations and detect transient absorption (TA) and TRCD spectra on a shot-to-shot basis simultaneously. We perform experiments on a squaraine polymer, investigating excitonic dynamics, and we develop a general theory for TRCD experiments of excitonically coupled systems that we then apply to describe the experimental data in this particular example. At a magic angle of 54.7° between the pump-pulse polarization and the propagation direction of the probe pulse, the TRCD and TA signals become particularly simple to analyze, since the orientational average over random orientations of complexes factorizes into that of the interaction with the pump and the probe pulse, and the intrinsic electric quadrupole contributions to the TRCD signal average to zero for isotropic samples. Application of exciton theory to linear absorption and to linear circular dichroism spectra of squaraine polymers reveals the presence of two fractions of polymer conformations, a dominant helical conformation with close interpigment distances that are suggested to lead to short-range contributions to site energy shifts and excitonic couplings of the squaraine molecules, and a fraction of unfolded random coils. Theory demonstrates that TRCD spectra of selectively excited helices can resolve state populations that are practically invisible in TA spectroscopy due to the small dipole strength of these states. A qualitative interpretation of TRCD and TA spectra in the spectral window investigated experimentally is offered. The 1 ps time component found in these spectra is related to the slow part of exciton relaxation obtained between states of the helix in the low-energy half of the exciton manifold. The dominant 140 ps time constant reflects the decay of excited states to the electronic ground state., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Prescription opioid misuse remains a significant cause of morbidity and mortality associated with drug overdose. Researchers, government agencies, public health interests, and professional organizations support the benefits of naloxone coprescribing for patients on chronic opioid therapy to prevent deaths from opioid overdose. However, gaps remain in the provision of naloxone to patients at risk. Currently, less than 1% of patients who should be prescribed naloxone with their opioid medications obtain a prescription for naloxone, illustrating an opportunity for health care providers to conduct thorough risk assessments for patients taking opioids and coprescribing naloxone to those at risk. There are documented barriers to the provision of naloxone for primary care providers, pharmacists, and patients. Managed care organizations have also created barriers. To better understand and evaluate trends in treatment, coverage, policies, and needs associated with providing health services to patients with substance use disorders, the Academy of Managed Care Pharmacy (AMCP) Addiction Advisory Group conducted a survey in 2019. Eighty percent of the managed behavioral health organizations and 47% of AMCP payer members who responded to the survey encouraged naloxone coprescribing in patients at high risk of overdose; however, no organizations require coprescribing. Health plans, managed care organizations, prescribers, pharmacists, patients, and others have important roles in decreasing the morbidity and mortality associated with opioid overdose. In particular, managed care organizations can take specific and meaningful actions to implement payment policies that improve naloxone coprescribing for patients at risk. In this article, opportunities have been outlined for managed care leadership that actively support public health policies for naloxone coprescribing, and 7 recommendations are presented. DISCLOSURES: The AMCP Addiction Advisory Group and the development of this article were supported by Alkermes and Precision Toxicology. Sponsors participated in the advisory group, which provided guidance in the development of the manuscript. Dharbhamalla is employed by AMCP. Skelton is a paid consultant working with AMCP.

Over the last four decades, the expanded patient care roles of pharmacists in the United States (U.S.) have increased focus on ensuring the implementation of processes to enhance continuing professional development within the profession. The transition from a model of continuing pharmacy education (CPE) to a model of continuing professional development (CPD) is still evolving. As pharmacists assume more complex roles in patient care delivery, particularly in community-based settings, the need to demonstrate and maintain professional competence becomes more critical. In addition, long-held processes for post-graduate education and licensure must also continue to adapt to meet these changing needs. Members of the pharmacy profession in the U.S. must adopt the concept of CPD and implement processes to support the thoughtful completion of professional development plans. Comprehensive, state-of-the-art technology solutions are available to assist pharmacists with understanding, implementing and applying CPD to their professional lives.

Objectives: To describe the views of pharmacists and student pharmacists regarding (1) aspects of life and experiences that provide professional and personal satisfaction and fulfillment, (2) causes of stress, and (3) needs related to maintaining satisfaction and fulfillment., Design: A generic qualitative research design was used for collecting data from 380 pharmacists and 332 student pharmacists who wrote responses to an online survey hosted by the American Pharmacists Association (APhA) from November 17 to December 2, 2018, using standard data collection procedures applied by that organization. APhA uses its member and affiliate data files as its sampling frame and limits the number of contacts per year for each person in those files. De-identified responses from those who volunteered to write comments were sent to the research team for analysis. A conventional content analysis approach was applied for analysis of the text. Analysts convened to discuss emergent themes and develop operational descriptions. Key segments of text that best represented each theme were identified. Personal presuppositions were disclosed and were useful for developing group consensus for theme identification and description. Rigor was supported through assessment of credibility, confirmability, intercoder checking, transferability, inductive thematic saturation, and authenticity., Setting and Participants: Participants are in the design since data already collected., Outcome Measures: Not applicable., Results: Findings showed that pharmacists and student pharmacists are able to recognize and pursue achievement, recognition, responsibility, advancement, relationship, esteem, self-actualization, meaning, and accomplishment in both their professional and personal lives. However, external factors such as "workism" and individual factors such as "moral distress" were identified as areas of improvement that are needed for well-being and resilience., Conclusion: Pharmacists' basic human needs are being met, but to improve well-being and resilience for pharmacists in both their professional and personal lives, there is a need for addressing both the external factors and individual factors that they encounter., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Social desirability and the fear of sanctions can deter survey respondents from responding truthfully to sensitive questions. Self-reports on norm breaking behavior such as shoplifting, non-voting, or tax evasion may thus be subject to considerable misreporting. To mitigate such response bias, various indirect question techniques, such as the randomized response technique (RRT), have been proposed. We evaluate the viability of several popular variants of the RRT, including the recently proposed crosswise-model RRT, by comparing respondents' self-reports on cheating in dice games to actual cheating behavior, thereby distinguishing between false negatives (underreporting) and false positives (overreporting). The study has been implemented as an online survey on Amazon Mechanical Turk (N = 6, 505). Our results from two validation designs indicate that the forced-response RRT and the unrelated-question RRT, as implemented in our survey, fail to reduce the level of misreporting compared to conventional direct questioning. For the crosswise-model RRT we do observe a reduction of false negatives. At the same time, however, there is a non-ignorable increase in false positives; a flaw that previous evaluation studies relying on comparative or aggregate-level validation could not detect. Overall, none of the evaluated indirect techniques outperformed conventional direct questioning. Furthermore, our study demonstrates the importance of identifying false negatives as well as false positives to avoid false conclusions about the validity of indirect sensitive question techniques., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The American Pharmacists Association (APhA) convened the Biologics and Biosimilars Stakeholder Conference on November 30, 2016, in Washington DC. The objectives of the Conference were to determine the key issues and challenges within the marketplace for biologics, follow-on biologics (FOBs), and biosimilars, identify potential roles and responsibilities of pharmacists regarding biologic and biosimilar medications, and identify actions or activities that pharmacists may take to optimize the safe and cost-effective use of biologics and biosimilars., Data Sources: National thought leaders and stakeholder representatives, including individuals from the Food and Drug Administration, Centers for Medicare and Medicaid Services, a private third-party payer, manufacturers, and several national organizations of health care professionals, participated in the conference. Information shared by this group was supplemented with relevant legal and regulatory information and published literature., Summary: Biologics play a valuable role in the treatment of numerous health conditions, but their associated costs, which tend to be greater than those of small-molecule drugs, place a burden on the health care system. Biosimilars (both noninterchangeable and interchangeable) are highly similar copies of the originator biologic and offer the potential to reduce costs and improve patient access to biological products by increasing treatment options and creating a more competitive market. Despite the potential benefits of biosimilars, certain factors may limit their uptake. The conference participants explored issues that different stakeholders think influence the use of biologics, including biosimilars, in the United States. Barriers included technology, prescriber-pharmacist communication, legislation and regulations, limited patient and health care practitioner knowledge of biological products, patient and health care practitioner perceptions of biosimilars, and evolving science or lack of long-term data. After participants identified issues, they discussed strategies to address these concerns, including the need to enhance the education of pharmacists, prescribers, and patients regarding biologic products, including biosimilars and FOBs; the passage of state laws and regulations that do not impede the use of biosimilars, including interchangeable biosimilars; the use of product-specific tracking information in electronic health records and surveillance systems; bidirectional communication among pharmacists, prescribers, and other members of the care team to support pharmacovigilance and the maintenance of accurate patient records; and the development of evidence-based third-party payer policies., Conclusion: Patient access to safe and cost-effective treatments is an important goal for the health care system. As the availability and use of biosimilars, including those determined to be interchangeable, increases, their potential to lower costs and improve patient access to treatment grows. However, the extent of such growth is, in part, dependent on various stakeholders' decisions to provide, pay for, or use these products in a safe and thoughtful manner. Ongoing stakeholder collaboration, educational activities, and review of current government or payer policies are required to optimize the uptake of biological products, including biosimilars., (Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objectives: The Community Pharmacy Residency Program (CPRP) Planning Committee convened to develop a vision and a strategic action plan for the advancement of community pharmacy residency training. Aligned with the profession's efforts to achieve provider status and expand access to care, the Future Vision and Action Plan for Community-based Residency Training will provide guidance, direction, and a strategic action plan for community-based residency training to ensure that the future needs of community-based pharmacist practitioners are met., Data Sources: National thought leaders, selected because of their leadership in pharmacy practice, academia, and residency training, served on the planning committee. The committee conducted a series of conference calls and an in-person strategic planning meeting held on January 13-14, 2015. Outcomes from the discussions were supplemented with related information from the literature. Results of a survey of CPRP directors and preceptors also informed the planning process., Summary: The vision and strategic action plan for community-based residency training is intended to advance training to meet the emerging needs of patients in communities that are served by the pharmacy profession. The group anticipated the advanced skills required of pharmacists serving as community-based pharmacist practitioners and the likely education, training and competencies required by future residency graduates in order to deliver these services. The vision reflects a transformation of community residency training, from CPRPs to community-based residency training, and embodies the concept that residency training should be primarily focused on training the individual pharmacist practitioner based on the needs of patients served within the community, and not on the physical location where pharmacy services are provided., Conclusion: The development of a vision statement, core values statements, and strategic action plan will provide support, guidance, and direction to the profession of pharmacy to continue the advancement and expansion of community-based residency training., (Published by Elsevier Inc.)

Objective: To improve key indicators of diabetes care by expanding a proven community-based model of care throughout high-risk areas in the United States., Design: Observational, multisite, pre-post comparison study., Setting: Federally qualified health centers, free clinics, employer worksites, community pharmacies, departments of health, physician offices, and other care facilities in 25 communities in 17 states from June 2011 through January 2013., Participants: 1,836 patients disproportionately affected by diabetes representing diverse ethnicities, insurance statuses, and social and economic backgrounds., Intervention: Pharmacists were integrated into local, interdisciplinary diabetes care teams and provided customized diabetes education and medication consultations to patients., Main Outcome Measures: Clinical measures included glycosylated hemoglobin (A1C), body mass index, systolic and diastolic blood pressures, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and total cholesterol. Process measures included smoking status, eye examination status, foot examination status, and influenza vaccine status., Results: Pharmacist patient care services for those underserved or disproportionately affected by diabetes resulted in a statistically significant and clinically relevant decrease in mean A1C levels (-0.8%). Other outcome indicators were below target levels at baseline and decreased significantly but not by clinically relevant amounts (LDL-C, -7.1 mg/dL; triglycerides, -23.7 mg/dL, and total cholesterol, -8.8 mg/dL). The mean increase in HDL-C (+0.6 mg/dL) was not statistically significant or clinically relevant. Among evaluable patients who were not at target for process measures at baseline, 51.7% of 453 patients received eye examinations, 72.0% of 271 patients received foot examinations, 41.7% of 307 patients received influenza vaccinations, and 9.3% patients of 270 quit smoking during the project. Of the communities involved in the study, 92% intend to sustain pharmacists' services., Conclusion: Project, Impact: Diabetes results show significant improvement in patients' clinical outcomes and demonstrate that all patients, even those with tremendous barriers to appropriate diabetes care, benefit from patient-centered, interdisciplinary health care teams that include pharmacists.

Objective: The aim of our study is to compare the prevalence of illicit drug use estimated through a technique referred to as the "crosswise model" (CM) with the results from conventional direct questioning (DQ)., Method: About 1,500 students from Tehran University of Medical Sciences 2009-2010 were first interviewed by DQ and, then three months later, by the CM., Result: The CM yielded significantly higher estimates than DQ for lifetime prevalence of use of any illicit drug (CM = 20.2%,DQ = 3.0%, p < .001) and for lifetime prevalence of use of opium or its residue (CM = 13.6%, DQ = 1.0%, p < .001). Also, for use of any illicit drug in the last month and use of opium or its residue in the last month, the CM yielded higher point estimates than DQ, although these differences were not significant (any drug: CM = 1.5%, DQ = 0.2%, p = .66; opium: CM = 3.8%, DQ = 0.0%, p = .21)., Conclusion: Our findings suggest that the CM is a fruitful data collection method for sensitive topics such as substance abuse.

Introduction: 12 chain community pharmacy sites located in two geographic areas with the United States implemented easy-to-administer memory screening assessments for patients with risk factors of cognitive memory decline and referred at-risk patients to their physicians., Aim of the Study: To evaluate the impact of a pharmacy-based cognitive memory screening and referral program, measure patient satisfaction with these advanced clinical services, and assess willingness to pay for cognitive memory screening services., Setting: 12 chain pharmacy sites located in two geographic areas--ten Fred Meyer Pharmacies located in the Portland, Oregon area and two Kerr Drug Pharmacies located in North Carolina., Method: Pharmacists were educated on Alzheimer's disease, trained on how to provide cognitive memory screening exams, and equipped with screening and documentation tools. Following each screening, pharmacist provided education and counseling to the patients and referred at-risk patients to physicians for follow-up as appropriate., Main Outcome Measures: Results of screenings; satisfaction of patients; willingness to pay., Results: Pharmacists delivered cognitive memory assessments to 161 patients from June to November 2008. 44.1 % of patients experienced at least one cognitive deficiency that required referral to a physician based on the screening conducted. The cognitive memory screening and referral program was highly regarded by patients who completed the satisfaction survey, with 98.4 % of respondents indicating that they were either very satisfied or satisfied with the program., Conclusion: Cognitive memory screening can be easily incorporated into clinical service offerings in community pharmacy practice and provides a valuable opportunity to identify patients at-risk and refer them to a physician for appropriate testing and diagnosis.

Introduction: Women represent a growing proportion of older people and experience increasing disability in their longer lives. Using a universally agreed definition of disability based on the International Classification of Functioning, Disability and Health, this paper examines how, apart from age, social and economic factors contribute to disability differences between older men and women., Methods: World Health Survey data were analyzed from 57 countries drawn from all income groups defined by the World Bank. The final sample comprises 63638 respondents aged 50 and older (28568 males and 35070 females). Item Response Theory was applied to derive a measure of disability which ensured cross country comparability. Individuals with scores at or above a threshold score were those who experienced significant difficulty in their everyday lives, irrespective of the underlying etiology. The population was then divided into "disabled" vs. "not disabled". We firstly computed disability prevalence for males and females by socio-demographic factors, secondly used multiple logistic regression to estimate the adjusted effects of each social determinant on disability for males and females, and thirdly used a variant of the Blinder-Oaxaca decomposition technique to partition the measured inequality in disability between males and females into the "explained" part that arises because of differences between males and females in terms of age and social and economic characteristics, and an "unexplained" part attributed to the differential effects of these characteristics., Results: Prevalence of disability among women compared with men aged 50+ years was 40.1% vs. 23.8%. Lower levels of education and economic status are associated with disability in women and men. Approximately 45% of the sex inequality in disability can be attributed to differences in the distribution of socio-demographic factors. Approximately 55% of the inequality results from differences in the effects of the determinants., Conclusions: There is an urgent need for data and methodologies that can identify how social, biological and other factors separately contribute to the health decrements facing men and women as they age. This study highlights the need for action to address social structures and institutional practices that impact unfairly on the health of older men and women.

Individuals differ not only in their background characteristics, but also in how they respond to a particular treatment, intervention, or stimulation. In particular, treatment effects may vary systematically by the propensity for treatment. In this paper, we discuss a practical approach to studying heterogeneous treatment effects as a function of the treatment propensity, under the same assumption commonly underlying regression analysis: ignorability. We describe one parametric method and two non-parametric methods for estimating interactions between treatment and the propensity for treatment. For the first method, we begin by estimating propensity scores for the probability of treatment given a set of observed covariates for each unit and construct balanced propensity score strata; we then estimate propensity score stratum-specific average treatment effects and evaluate a trend across them. For the second method, we match control units to treated units based on the propensity score and transform the data into treatment-control comparisons at the most elementary level at which such comparisons can be constructed; we then estimate treatment effects as a function of the propensity score by fitting a non-parametric model as a smoothing device. For the third method, we first estimate non-parametric regressions of the outcome variable as a function of the propensity score separately for treated units and for control units and then take the difference between the two non-parametric regressions. We illustrate the application of these methods with an empirical example of the effects of college attendance on womens fertility.

Objectives: To identify the current challenges and opportunities in compensation and recognition for pharmacist-provided immunizations across the lifespan and to establish guiding principles for pharmacist-provided immunization compensation and recognition., Data Sources: 22 stakeholders gathered on June 29, 2011, at the American Pharmacists Association (APhA) headquarters in Washington, DC, for a meeting on immunization compensation that was convened by APhA and the Academy of Managed Care Pharmacy. Participants included representatives from community pharmacy practices (chain, grocery, and independent), employers, national consumer health and advocacy organizations, national pharmacy and public health organizations, health plan representatives, pharmacy benefit managers, and health information technology, standards, and safety organizations. Key immunization leaders from TRICARE Management Activity, the Centers for Medicare & Medicaid Services, the National Vaccine Program Office of the Department of Health & Human Services, and the Centers for Disease Control and Prevention (CDC) also participated in the meeting., Summary: The increased numbers of pharmacists providing vaccination services and the availability of pharmacist-provided immunizations to populations in need of vaccines has continued to increase. This has resulted in a rise in the percentage of patients who receive vaccines at pharmacies. Pharmacists are now working to lever-age their ability to identify people with key risk factors (e.g., diabetes, heart disease or previous myocardial infarction), encourage them to receive their CDC-recommended vaccinations, and administer the required vaccine. Challenges and opportunities in compensation and recognition for pharmacist-provided immunizations across the adult lifespan persist. Variability in state practice acts, reimbursement and compensation processes and systems, and mechanisms for documentation of vaccine services create substantial differences in how pharmacist-provided immunizations are delivered throughout the United States., Conclusion: Pharmacist-provided immunizations are clinically sound, are cost effective, are readily accessible, and support our nation's public health goals. Pharmacists have demonstrated that patient vaccination rates have improved through expansion of pharmacist-provided immunizations. The profession should continue efforts to collaborate with other immunization stakeholders and expand a pharmacist scope of practice that is built around a uniform and recognized standard of immunization provision and that supports the provision of all CDC-recommended vaccines through pharmacy-provided immunizations.

Objective: The purpose of this initiative was to establish a Coordinating Council to Improve Collaboration in Supporting Patients with Alzheimer's Disease. The Council convened on March 5-6, 2008, in Washington, DC. The American Pharmacists Association (APhA) Foundation, in conjunction with leading national experts in Alzheimer's disease (AD), assessed the level of care and services currently provided by pharmacists to AD patients and developed this "blueprint document" for how they might be more effective in helping patients and family caregivers manage the burden of this devastating disease., Data Source: A premeeting survey of Council members was conducted to elicit their perceptions regarding the needs and challenges facing AD patients and their family caregivers and to gain insights as to what roles pharmacists could and should be playing to help manage drug therapy and enhance the quality of life in patients with AD., Summary: AD is one of the most significant health crises that will be faced in the United States over the next 30 years. Currently, it is the sixth leading cause of death in the country. The findings of the Council confirmed that pharmacists are playing important roles in the management of AD but can expand these roles., Conclusion: Pharmacists are accessible, trusted, and respected resources. Increased pharmacist involvement in the care of individuals with AD could improve clinical outcomes and family caregiver quality of life. With the expected increase in the number of individuals diagnosed with AD, the resources and services to care for and support this population will be even further taxed. Innovative approaches for expanding pharmacist involvement in AD should be developed to maximize the difference pharmacists can make in the lives of those who suffer from the disease.

Individuals who have hemineglect fail to attend to stimuli presented on the side of the body contralateral to a brain lesion. Although in animal studies the severity of neglect correlates with the degree of dopamine depletion, in hemineglect patients dopamine-enhancing medications have produced inconsistent results. We present a case of hemineglect following a right cerebrovascular accident in a 68-year-old man treated consecutively with methylphenidate and bromocriptine. Tests sensitive to neglect were administered during treatment with methylphenidate, then after all medications had been discontinued, then when the patient was taking low and moderate doses of bromocriptine, and again after all medications had been discontinued for 4 and 26 days. Methylphenidate was superior to no drug treatment. Bromocriptine produced more improvement in neglect than methylphenidate. Although the patient showed an exacerbation of his neglect after withdrawal from methylphenidate, performance gains persisted after withdrawal from bromocriptine. Treatment effects appear related to medication choice, timing of drug treatment, and the adaptability of dopaminergic receptor systems.

There is mounting evidence that human muscles have discrete partitions. In an effort to accurately assess how the control to each of the three heads (designated as A-C) of the lateral gastrocnemius (LG) muscle might be organized, we performed exploratory studies in five subjects each of whom was provided 30 random angular and linear perturbations while standing on a balance platform in each of three experiments. The responses from each LG head were recorded with strategically-placed fine-wire electrodes and, after correction for variation in distance to each recording site, latency to activation and the sequence of recruitment for each LG head were determined. Within individual subjects, the same LG head was first recruited. The C-head was recruited first during linear perturbations between subjects and across sessions, but the overall recruitment pattern was different between subjects. The fact that a consistent, selective response was seen during dynamic linear but not angular perturbations suggests that a more consistent strategy of inter-partition response may be engaged for the former perturbation. This behaviour may be caused by use of the LG C-head to assist the medial gastrocnemius to control ankle plantar flexion and pronation during the shearing forces generated with linear translations. Further exploration into the relationship between selective activation of muscle partitions in the presence of defined movement conditions appears justified.

The capsular K5 polysaccharide of Escherichia coli is the receptor of the capsule-specific coliphage K5, which harbors an enzyme that degrades the capsular K5 polysaccharide to a number of oligosaccharides. Analysis of the degradation products using gel permeation chromatography, the periodate-thiobarbituric acid and bicinchoninic acid reactions, and nuclear magnetic resonance spectroscopy showed that the major reaction products are hexa-, octa-, and decasaccharides with 4,5-unsaturated glucuronic acid (delta4,5GlcA) at their nonreducing end. Thus, the bacteriophage enzyme is a K5 polysaccharide lyase and not, as we had reported previously, an endo-N-acetylglucosaminidase.

The structures of the 6-deoxytalose-containing O-specific polysaccharides from the O45 antigen, an O45-related antigen (O45rel), and the O66 antigen (lipopolysaccharides, LPSs) of Escherichia coli were elucidated by chemical characterization and by one- and two-dimensional 1H and 13C NMR spectroscopy. The O45 and O45-related polysaccharides have the following general structure: [formula: see text] For the O45 antigen, X is alpha-D-FucpNAc and for the O45-related antigen, X is beta-D-GlcpNAc. The structure of the O66 polysaccharide is [formula: see text]

Structures for the N-acetylneuraminic acid (Neu5Ac)-containing O56 and O24 polysaccharides of Escherichia coli have been reported previously. During these studies unusual chemical shifts had been observed for the NMR signals for H-3eq and C-3 of the Neu5Ac residues of both polysaccharides. In further pursuing this phenomenon, we have reinvestigated the O56 and O24 polysaccharides as well as derived oligosaccharides by one- and two-dimensional NMR spectroscopy. The results showed that structures of both polysaccharides (PSs) had to be modified and formulated as [formula: see text] 2D ROESY spectra revealed a strong NOE between H-3eq of Neu5Ac and the protons of the side-chain sugar (H-3 and H-5 of alpha-D-Gal p in the O56 PS and H-3 of alpha-D-Glc p in the O24 PS) and also between H-3ax of Neu5Ac and H-3 of beta-D-Glc p in the main chain. This indicated a close spatial association of the seven-linked alpha-Neu5Ac and the side-chain residues alpha-D-Gal p (O56 PS) and alpha-D-Glc p (O25 PS), respectively. The strong long-range spatial contacts caused the unusual chemical shifts of H-3eq and C-3 of Neu5Ac.

In a previous report, we described heretofore undiscovered possibilities that neuropathic pain and spasticity may share some common pathophysiological mechanisms. Currently, systemically delivered local anesthetics are being used for the evaluation and treatment of neuropathic pain. We present a case describing the treatment of spasticity of spinal origin with continuous subcutaneous infusion of 0.75% bupivacaine in a patient who did not respond to traditional treatments and has become tolerant to intrathecal baclofen.

The polysaccharide moiety of the O16 antigen (lipopolysaccharide) consists of D-glucopyranose, D-galactofuranose, L-rhamnopyranose, and 2-acetamido-2-deoxy-D-glucopyranose in the molar ratios 1:1:1:1. It is O-acetylated with one acetyl group per repeating unit. One- and two-dimensional NMR spectroscopy of the polysaccharide before and after O-deacetylation showed that the O16 polysaccharide has the structure [formula: see text]

Expression of the Escherichia coli K5 antigen was used as a model system to study the role of known regulators of gene expression on production of group II capsules in E. coli. Only mutations in the rfaH gene had an effect on production of the K5 antigen, abolishing the expression of any detectable capsule at 37 degrees C. None of the mutations studied induced capsule expression at 18 degrees C. A sequence, termed JUMPstart, found in group II capsule gene clusters and upstream of a number of polysaccharide biosynthesis genes in enteric bacteria is homologous to sequences found in RfaH regulated operons. This may indicate a common mode of regulation of these polysaccharide biosynthesis genes by RfaH.

Two distinct forms of the O6 antigen (LPS) from E. coli were analysed using 1H and 13C NMR spectroscopy. Their structures were found to be [formula: see text] In the O6-specific polysaccharide from E. coli O6:K2 and O6:K13, X is beta-D-Glc p, as had previously been shown for the O6 polysaccharide from E. coli O6:K15; in the O6 specific polysaccharide from E. coli O6:K54, X is beta-D-Glc pNAc.

The polysaccharide moiety of the O83 antigen (lipopolysaccharide, LPS) consists of D-glucose, D-galactose, 2-acetamido-2-deoxy-D-glucose, and D-glucuronic acid in the molar ratios 1:2:1:1. Methylation analysis of the polysaccharide and derived oligosaccharides as well as one- and two-dimensional 1H and 13C NMR spectroscopy of the polysaccharide at pD 1 and 6 showed that the O83 polysaccharide has the primary structure-->6)-alpha-D-Glc p-(1-->4)-beta-D-Glc pA-(1-->6)-beta-D-Gal p-(1-->4)-beta-D- Gal p-(1-->4)-beta-D-Glc pNAc-(1-->.

This study examined the neurobehavioural effects of closed head injury (CHI) in adults aged 50 years and older. Twenty two mild to moderate CHI patients who were within seven months of the injury were administered measures of language, memory, attention, and executive functioning. Compared with demographically similar normal controls, the patients exhibited significantly poorer functioning on the cognitive domains. Naming and word fluency under timed conditions, verbal and visual memory, and the ability to infer similarities were especially vulnerable. These initial findings indicate that CHI in older adults produces considerable cognitive deficits in the early stages of recovery. Future research should characterise long term outcome and the potential links between head injury and the development of progressive dementia.

The polysaccharide moiety of the O22-antigen (lipopolysaccharide, LPS) consists of 2-acetamido-2-deoxy-D-galactose, D-glucuronic acid, D-glucose, and D-galactose in the molar ratios 2:1:1:1. Methylation analysis as well as 1D and 2D NMR spectroscopy showed that the O22 polysaccharide has the primary structure [formula: see text]

Subcloning, transposon insertion, and deletion analysis revealed that the Escherichia coli O9 rfb region is about 12 kb in size. The region encodes at least seven polypeptides of 89, 74, 55, 50, 44, 41 and 39.5 kDa. Southern hybridization analysis of rfb regions of E. coli O8 and O9, and Klebsiella O3 and O5 serotypes (all of these O polysaccharides are mannose homopolymers and the structures of the repeating unit of E. coli O9 and Klebsiella O3 are identical) showed that a central region specific for E. coli O9 and Klebsiella O3 is flanked by two regions common to all four. Complementation experiments using strains with known defects and specific tests for the enzymic activity showed that the 50 and 55 kDa polypeptides, encoded by the common region, are phosphomannomutase (PMM) and GDP-mannose pyrophosphorylase (GMP), respectively. Nucleotide sequencing of the region revealed the presence of two genes, rfbK and rfbM, analogous to the corresponding genes of Salmonella typhimurium. In E. coli O9, rfbK and rfbM encode proteins of 460 amino acids (50,809 Da) and 471 amino acids (52,789 Da). The amino acid sequence of GMP was conserved in RfbMs of E. coli O7 and Salmonella groups B, C1 and C2, CpsB of S. typhimurium, AlgA of Pseudomonas aeruginosa, and XanB of Xanthomonas campestris. The phylogenetic trees of PMM and GMP were different in topology and in the evolutionary distances from ancestors.

The genes directing the expression of group II capsules in Escherichia coli are organized into three regions. The central region 2 is type specific and thought to determine the synthesis of the respective polysaccharide, whilst the flanking regions 1 and 3 are common to all group II gene clusters and direct the surface expression of the capsular polysaccharide. In this communication we analyze the involvement of region 1 and 3 genes in the synthesis of the capsular KS polysaccharide. Recombinant E. coli strains harboring all KS specific region 2 genes and having various combinations of region 1 and 3 genes were studied using immunoelectron microscopy. Membranes from these bacteria were incubated with UDP[14C]GlcA and UDPGlcNAc in the absence or presence of KS polysaccharide as an exogenous acceptor. It was found that recombinant strains with only gene region 2 did not produce the K5 polysaccharide. Membranes of such strains did not synthesize the polymer and did not elongate K5 polysaccharide added as an exogenous acceptor. An involvement of genes from region 1 (notably kpsC and kpsS) and from region 3 (notably kpsT) in the K5 polysaccharide synthesis was apparent and is discussed.

Two distinct forms of the O4 antigen (LPS) from E. coli were analysed by 1H and 13C NMR spectroscopy. Both consisted of D-glucose, L-rhamnose, 2-acetamido-2,6-dideoxy-L-galactose (L-FucNAc), and 2-acetamido-2-deoxy-D-glucose. Their structures were found to be [formula: see text]. In the O4-specific polysaccharide from E. coli O4:K3, O4:K6, and O4:K12, X is alpha-D-Glcp. In the O4 specific polysaccharide from E. coli O4:K52, the rhamnose residue is not substituted (X = H).

The polysaccharide moiety of the O23 antigen (lipopolysaccharide) consists of D-glucose, D-galactose, 2-acetamido-2-deoxy-D-glucose, and 2-acetamido-2-deoxy-D-galactose in the molar ratios 2:1:2:1. Methylation analysis of the polysaccharide as well as one- and two-dimensional 1H and 13C NMR spectroscopy of the polysaccharide and a trisaccharide obtained by Smith degradation showed that the O23 polysaccharide has the primary structure [formula: see text].

A computer evaluation of 13C-NMR data for the title polysaccharides based on the monosaccharide and methylation analysis data led to the structure of the repeating unit of the O1A polysaccharide as well as to several probable structures of the O1C polysaccharide, of which the correct one was inferred by means of a single NOE experiment. The analysis of the spectrum of the O1B polysaccharide was unsuccessful, due to the presence in its structure of the fragment alpha-L-Rha-(1-->2)-alpha-D-Gal-(1-->3)-D-GlcNAc with the terminal (1-->2)-linkage, whose spectral data could not be calculated by additive schemes using only glycosylation effects. However in reevaluation of the O1B spectral data by taking into account the deviations from additivities of the chemical shifts values in spectra of the related trisaccharides, to reveal the most probable structure of the O1B's repeating unit. [formula: see text]

In Escherichia coli K-12, the rcsA and rcsB gene products are positive regulators in expression of the slime polysaccharide colanic acid. We have previously demonstrated the presence of rcsA sequences in E. coli K1 and K5, strains with group II capsular K antigens, and shown that introduction of multicopy rcsA into these strains results in the expression of colanic acid. We report here the presence of rcsB sequences in E. coli K1 and K5 and demonstrate that RcsB also plays a role in the biosynthesis of colanic acid in strains with group II K antigens. In E. coli K1 and K5 grown at 37 degrees C, multicopy rcsB and the resulting induction of colanic acid synthesis had no significant effect on synthesis of the group II K antigens. K-antigen-specific sugar transferase activities were not significantly different in the presence or absence of multicopy rcsB, and introduction of a cps mutation to eliminate colanic acid biosynthesis in a K1-derivative strain did not influence the activity of the polysialyltransferase enzyme responsible for synthesis of the K1 polymer. Furthermore, immunoelectron microscopy showed no detectable difference in the size or distribution of the group II K-antigen capsular layer in cells which produced colanic acid. Colanic acid expression therefore does not appear to significantly affect synthesis of the group II K-antigen capsule and, unlike for group I K antigens, expression of group II K antigens is not positively regulated by the rcs system.

The gene cluster of the capsular K5 polysaccharide, a representative of group II capsular antigens of Escherichia coli, has been cloned previously, and three regions responsible for polymerization and surface expression have been defined (I.S. Roberts, R. Mountford, R. Hodge, K. B. Jann, and G. J. Boulnois, J. Bacteriol. 170:1305-1330, 1988). Region 1 has now been sequenced, and five open reading frames (kpsEDUCS) have been defined (C. Pazzani, C. Rosenow, G. J. Boulnois, D. Bronner, K. Jann, and I. S. Roberts, J. Bacteriol. 175:5978-5983, 1993). In this study, we characterized region 1 mutants by immunoelectron microscopy, membrane-associated polymerization activity, cytoplasmic CMP-2-keto-3-deoxyoctonate (KDO) synthetase activity, and chemical analysis of their K5 polysaccharides. Certain mutations within region 1 not only effected polysaccharide transport (lack of region 1 gene products) but also impaired the polymerization capacity of the respective membranes, reflected in reduced amounts of polysaccharide but not in its chain length. KDO and phosphatidic acid (phosphatidyl-KDO) substitution was found with extracellular and periplasmic polysaccharide and not with cytoplasmic polysaccharide. This and the fact that the K5 polysaccharide is formed in a kpsU mutant (defective in capsule-specific K-CMP-KDO synthetase) showed that CMP-KDO is engaged not in initiation of polymerization but in translocation of the polysaccharide.

The K10 antigen from Escherichia coli O11:K10:H10 consists of equimolar amounts of rhamnose and 4,6-dideoxy-4-malonylaminoglucose [Qui4NMal; 4-(2-carboxyacetamido)-4,6-dideoxyglucose]. Methylation analysis and 1 and 2D NMR spectroscopy showed that the K10 capsular polysaccharide has the structure [formula: see text]

Activity progression of persons with physical disabilities and accompanying cardiovascular disease in medical rehabilitation centers is traditionally based on cardiac precautions derived from acute care settings. Concern that these guidelines were too conservative and restrictive led to exercise testing and evaluation of 64 physically disabled male patients with a history of coronary artery disease. The sample had a mean age of 62.4 years. The exercise test was an adaptation of the Schwade Arm Ergometer Protocol with blood pressure measured at baseline, immediately after each 2 minutes of exercise, peak exercise and each minute for 6 minutes after peak exercise. Heart rate was monitored continuously. Patients achieved a mean peak heart rate of 115 beats per minute, mean peak systolic pressure of 169 mm Hg and mean peak diastolic pressure of 89 mm Hg. Ischemic electrocardiographic changes occurred in four of the 64 patients. Based on the achieved ranges of values of heart rate, systolic and diastolic pressures and comparison of these results with baseline (pre-exercise) values, more liberal guidelines for prescribing activity in the non-acute inpatient setting are provided.

In previous studies it had been shown that lipopolysaccharide from O4-specific recombinant Escherichia coli, had serological reactivities and a chemical composition that differed from wildtype O4 LPS [Haraguchi, G.E., Zähringer, U., Jann, B., Jann, K., Hull, R.A. & Hull, S.I. (1991) Microb. Pathog. 10, 351-361]. Here we present the structural elucidation of the O-specific moieties from lipopolysaccharides of some of the recombinant strains obtained in previous studies. Compositional analysis, methylation, chemical reactions and NMR spectroscopy showed that, during genetic manipulations (recombination, cosmid cloning, plasmid subcloning), a gradual structural change in the O-specific polysaccharides was observed in the recombinant strains. These changes comprised of an alteration in the position of glucose (side chain) substitution, a change in the anomeric configuration of the main-chain N-acetylglucosamine and an exchange of alpha-L-rhamnopyranose for beta-D-galactofuranose. The relevance of these results for lipopolysaccharide cloning and lipopolysaccharide biosynthesis are discussed.

The O56 polysaccharide moiety of the O56 antigen (LPS) consists of D-glucose, D-galactose, 2-acetamido-2-deoxy-D-glucose, and N-acetylneuraminic acid in the molar ratios 1:1:1:1. Methylation analysis, periodate oxidation, mild acid hydrolysis, as well as 1H and 13C NMR spectroscopy showed that the O56 polysaccharide has the primary structure [formula: see text]

Ethical issues pertaining to treating pediatric rehabilitation patients stem from at least three sources: the fact that children are not morally autonomous persons and must depend on the values and moral beliefs of others in ethically complex decision-making situations; the extent of parental authority in asserting problematic beliefs or imposing questionable demands affecting treatment decisions; and the way clinical uncertainty affects moral uncertainty in determining treatment approaches or alternatives. Although these problems are pervasive among all age groups of children with disabilities, this article will primarily examine their impact on the rehabilitation of children and adolescents. Principles and strategies for managing value-laden conflicts will be discussed along with how various ethical, social, and clinical constraints may nevertheless compromise a straightforward resolution of an ethically vexing situation.

The primary structure of an emulsion-stabilizing exopolysaccharide from the adhesive, hydrophobic Rhodococcus strain No. 33 was elucidated by NMR spectroscopy, methylation analyses, periodate oxidation and oligosaccharide analyses. The polysaccharide PS-33 consisted of rhamnose, galactose, glucose and glucuronic acid in molar ratios of 2:1:1:1. The main chain contained 3-substituted alpha-D-glucuronic acid linked to the 3-position at alpha-L-rhamnose, in addition to 3-substituted residues of beta-D-galactose and alpha-D-glucose. The alpha-L-rhamnose of the side chain was linked to position 4 of the galactose. In addition, the polysaccharide was O-acetylated, corresponding to one acetyl group per repeating unit. From the results two structural possibilities could be suggested. As the polysaccharide carries hydrophobic groups (methyl of rhamnose/O-acetyl), it is very likely that these are of general significance for the emulsifying activity of polysaccharides. It also seems to be possible that this polysaccharide is at least partially responsible for the hydrophobic cell surface properties of the Rhodococcus strain No. 33 and it may be involved in hydrophobic interactions when adhering to hydrophobic interfaces.

The O-specific moieties of the O1B antigen (lipopolysaccharide) from Escherichia coli O1B:K1 and the O1C antigen from E. coli O1C:K- both consist of L-rhamnose, D-galactose, N-acetyl-D-glucosamine, and N-acetyl-D-mannosamine in a molar ratio of 2:1:1:1. By using fragmentation procedures, methylation analysis, and one- and two-dimensional nuclear magnetic resonance spectroscopy, the structures of these polysaccharides were found to be [formula: see text] In the O1B polysaccharide X is 2, and in the O1C polysaccharide X is 3. With the recently published structure of the O1A polysaccharides (B. Jann, A. S. Shashkov, D. S. Gupta, S. M. Panasenko, and K. Jann, Carbohydr. Polym. 18:51-57 1992), three related O1 antigens are now known. Their common (O1-specific) epitope is suggested to be the side-chain N-acetyl-D-mannosamine residue.

The O-specific polysaccharide moieties (PS) of the O18A, O18A1, O18B, and O18B1 antigens (lipopolysaccharides, LPS) consist of L-rhamnose (Rha), N-acetyl-D-glucosamine, D-galactose, and D-glucose in different molar ratios. By using chemical fragmentation, methylation, as well as one- and two-dimensional NMR spectroscopy, the structures of these polysaccharides were found to be [formula: see text] In O18A-PS and O18A1-PS x = 2, whereas in O18B-PS and in O18B11-PS x = 3. In all four polysaccharides alpha-D-Galp (residue D) is substituted at O-3. This substituent L (residue E) is beta-D-GlcpNAc-(1 in O18A-PS and O18A1-PS and it is alpha-D-Glcp-(1 in O18B-PS and O18B1-PS. Whereas there is no further substituent on the main chain of the O18A and O18B polysaccharides, in O18A1-PS and O18B1-PS the alpha-D-GlcpNAc residue A is substituted with alpha-Glcp-(1 (residue F), which is linked to O-6 in O18A1-PS and to O-4 in O18B1-PS. These results show that the O18 antigen comprises a group of four related LPS (O18A and O18B, with their glucosylated forms O18A1 and O18B1). The results are discussed with respect to epitope definition and biochemical implications.