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Highlights • While optic nerves are part of the CSI target volume, lenses need to be spared. • Lens and optic disc movement for different gaze directions was evaluated in MRI scans. • Eye movement influence on lens and optic nerve CSI dose distribution was analyzed. • With modern radiotherapy techniques, any eye movement increases the mean lens dose. • Maximum eye movements decrease mean orbital optic nerve D98, Purpose Optic nerves are part of the craniospinal irradiation (CSI) target volume. Modern radiotherapy techniques achieve highly conformal target doses while avoiding organs-at-risk such as the lens. The magnitude of eye movement and its influence on CSI target- and avoidance volumes are unclear. We aimed to evaluate the movement-range of lenses and optic nerves and its influence on dose distribution of several planning techniques. Methods Ten volunteers underwent MRI scans in various gaze directions (neutral, left, right, cranial, caudal). Lenses, orbital optic nerves, optic discs and CSI target volumes were delineated. 36-Gy cranial irradiation plans were constructed on synthetic CT images in neutral gaze, with Volumetric Modulated Arc Therapy, pencil-beam scanning proton therapy, and 3D-conventional photons. Movement-amplitudes of lenses and optic discs were analyzed, and influence of gaze direction on lens and orbital optic nerve dose distribution. Results Mean eye structures’ shift from neutral position was greatest in caudal gaze; −5.8±1.2 mm (±SD) for lenses and 7.0±2.0 mm for optic discs. In 3D-conventional plans, caudal gaze decreased Mean Lens Dose (MLD). In VMAT and proton plans, eye movements mainly increased MLD and diminished D98 orbital optic nerve (D98OON) coverage; mean MLD increased up to 5.5 Gy [total ΔMLD range −8.1 to 10.0 Gy], and mean D98OON decreased up to 3.3 Gy [total ΔD98OON range −13.6 to 1.2 Gy]. VMAT plans optimized for optic disc Internal Target Volume and lens Planning organ-at-Risk Volume resulted in higher MLD over gaze directions. D98OON became ≥95% of prescribed dose over 95/100 evaluated gaze directions, while all-gaze bilateral D98OON significantly changed in 1 of 10 volunteers. Conclusion With modern CSI techniques, eye movements result in higher lens doses and a mean detriment for orbital optic nerve dose coverage of

Background: The SIOPE-Brain Tumor Group recently published a guideline on craniospinal target volume delineation for highly conformal radiotherapy. In order to spare critical structures like e.g., the lens or cochlea, highly conformal techniques can underdose the cerebrospinal fluid (CSF) in the dural reflections around cranial and sacral nerves. The purpose of this study is to generate evidence for CSF extension within the dural sheaths of the cranial and sacral nerves in order to improve accuracy in target volume delineation. Material and methods: Ten healthy volunteers, age 21 till 41 years, underwent an MRI-scan of the skull-base and sacral plexus. To evaluate CSF extension, cT2-weighted images with fat suppression, low signal to noise ratio and little to no motion-related artifacts were used. Two observers measured the extension of CSF from the inner table of the skull for the cranial nerves, and outside the spinal canal for the sacral nerves. Results: CSF extension (mean distance [95% CI]) was visible within the dural sheaths surrounding the majority of the cranial nerves: optic nerve (40 mm [38–42]), trigeminal nerve (16 mm [15–19]), facial-vestibulocochlear nerve (11 mm [11–12]), glossopharyngeal-vagus-accessory nerve (7 mm [7–9]) and hypoglossal nerve (8 mm [7–9]). No CSF was observed outside the spinal canal at sacral level. No significant difference between both observers was measured. Conclusion: This study generates evidence for significant CSF extension outside the inner table of the skull. Despite the vicinity of the lens and cochlea, we therefore recommend the inclusion of both optic nerves and internal auditory canals in the clinical target volume for craniospinal irradiation when using highly conformal delivery techniques.

Renal osteodystrophy is a common complication of end-stage renal failure patients. It's most severe osseous complication is characterized by massive thickening of the cranial vault and facial bones, called uremic leontiasis ossea (ULO), with only few cases reported in the literature. A case of a 47-year-old female patient with ULO is presented. Physical examination showed enlargement of the jaws, which hinders proper ventilation and feeding. The computed tomography examination showed marked osseous proliferation in the jaws causing severe bony expansion and loss of normal bony architecture in the skull and the skull base. The most relevant clinical, histopathological and laboratory findings are discussed. The uremic leontiasis ossea causes significant aesthetic and functional changes. Correct diagnosis and management of the factors responsible for the development of bone lesions due to altered bone metabolism are key factors. The maxillofacial surgeon must have the proper knowledge of patient's medical condition and bone maturation status to address an adequate surgical strategy.

Researchers have proposed a variety of behavioral traits that may lead to weight gain and obesity; however, little is known about the neurocognitive mechanisms underlying these weight-related eating behaviors. In this study, we measured activation of reward circuitry during a task requiring response and inhibition to food stimuli. We assessed participants’ emotional eating, external eating, and two subscales of dietary restraint—routine restraint and compensatory restraint—using the Weight-Related Eating Questionnaire. For routine restraint, we found positive associations with activation in the insula, dorsolateral prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex and ventromedial prefrontal cortex in response to high-calorie versus low-calorie foods. For emotional eating, we found positive associations with insula and dorsolateral prefrontal cortex activation in response to high-calorie versus low-calorie foods. We also found positive associations between emotional eating and dorsolateral prefrontal cortex activation in response to approach versus inhibition towards high-calorie foods. Thus, our results demonstrate an increase in activation across brain regions related to self-control and urges in response to high-calorie food associated with both emotional eating and routine restraint. Overall, these results support the construct validity of both emotional eating and routine restraint and provide preliminary evidence that these subscales have similar neural correlates.

A feminist analysis of the Sloyd crafting education movement reveals how it contributed to the transformation of Western culture’s foundational gender system. The Sloyd movement transformed traditional domestic crafts in patriarchal families into formal manual education courses and programs that were disseminated around the globe at the turn of the twentieth century. Feminist understanding of the historical context of European patriarchy is essential in appreciating how Sloyd programs contributed to reform women’s transformations of patriarchal ideology and social structures. The Sloyd educational movement could not have developed without the prior development of public schools with manual education. Feminist critical reading was required to gender largely de-gendered histories of European manual education and the development of the Sloyd movement. Feminist theories, methods, and research have provided insights into the importance of the Sloyd crafting education movement in materially transforming gender roles, identities, ideology, and social power dynamics.

Background The Practice Management Committee (PMC) of the Pediatric Endocrine Society (PES) conducted a survey of its membership in February/March, 2016 to assess the current state of pediatric diabetes care delivery across multiple practice types in the United States. Methods The PES distributed an anonymous electronic survey (Survey Monkey) via email to its membership and requested that only one survey be completed for each practice. Results Ninety-three unique entries from the US were entered into analysis. Care is predominantly delivered by multidisciplinary teams, based at academic institutions (65.6%), with >85% of the provider types being physicians. Each 1.0 full time equivalent certified diabetes educators serves on average 367 diabetic youth. Fee-for-service remains the standard method of reimbursement with 57% of practices reporting financial loss. Survey respondents identified under-reimbursement as a major barrier to improving patient outcomes and lack of behavioral health (BH) providers as a key gap in services provided. Conclusions Our survey reveals wide variation in all aspects of pediatric diabetes care delivery in the United States. Pediatric Endocrinologists responding to the survey identified a lack of resources and the current fee for service payment model as a major impediment to practice and the lack of integrated BH staff as a key gap in service. The respondents strongly support its organizations' involvement in the dissemination of standards for care delivery and advocacy for a national payment model aligned with chronic diabetes care in the context of our emerging value-based healthcare system.

Summary Background Drug interaction references report that initiation of levothyroxine potentiates the effects of warfarin, and recommend more frequent International Normalized Ratio (INR) monitoring, but the mechanism is not well understood. Objective To assess the impact of levothyroxine initiation on INR response. Patients/Methods A retrospective, self-controlled study was performed on patients aged ≥ 18 years receiving chronic warfarin therapy who were started on levothyroxine between 1 January 2006 and 30 June 2013, and who were followed for 90 days prior to and after levothyroxine initiation. The included patients had at least one elevated thyroid-stimulating hormone laboratory value in the pre-period, continuous warfarin therapy for 100 days prior to levothyroxine initiation, no purchases of medications known to interact with warfarin, no procedures requiring warfarin interruption, and no bleeding or thromboembolic event during the study period. The primary outcome was a comparison of the warfarin dose/INR ratio recorded before the initiation of levothyroxine with the ratio recorded during the post-period after two consecutive INRs with no warfarin dose change. Results One hundred and two patients were included in the primary outcome. The mean warfarin dose/INR ratios in the pre-period and post-period were equivalent (P = 0.825). Although the mean warfarin dose was numerically lower in the post-period than in the pre-period, this difference did not reach statistical significance (P = 0.068). Conclusion No difference in the mean warfarin dose/INR ratio before and after initiation of levothyroxine was detected. The results suggest that there is not a clinically significant interaction between warfarin and levothyroxine, and so additional monitoring may not be necessary.

Of the five muscarinic receptor subtypes, the M5receptor is the only one detectable in midbrain dopaminergic neurons, making it an attractive potential therapeutic target for treating disorders in which dopaminergic signaling is disrupted. However, developing an understanding of the role of M5in regulating midbrain dopamine neuron function has been hampered by a lack of subtype-selective compounds. Here, we extensively characterize the novel compound VU0238429 and demonstrate that it acts as a positive allosteric modulator with unprecedented selectivity for the M5receptor. We then used VU0238429, along with M5knock-out mice, to elucidate the role of this receptor in regulating substantia nigra pars compacta (SNc) neuron physiology in both mice and rats. In sagittal brain slices that isolate the SNc soma from their striatal terminals, activation of muscarinic receptors induced Ca2+mobilization and inward currents in SNc dopamine neurons, both of which were potentiated by VU0238429 and absent in M5knock-out mice. Activation of M5also increased the spontaneous firing rate of SNc neurons, suggesting that activation of somatodendritic M5increases the intrinsic excitability of SNc neurons. However, in coronal slices of the striatum, potentiation of M5with VU0238429 resulted in an inhibition in dopamine release as monitored with fast scan cyclic voltammetry. Accordingly, activation of M5can lead to opposing physiological outcomes depending on the location of the receptor. Although activation of somatodendritic M5receptors on SNc neurons leads to increased neuronal firing, activation of M5receptors in the striatum induces an inhibition in dopamine release.

Nitric oxide (NO) synthesis in endothelial cells is impaired in diabetes. We previously showed that impaired NO synthesis in the spontaneously diabetic BB (BBd) rat is due to decreased levels of tetrahydrobiopterin (BH4), secondary to decreased expression of GTP cyclohydrolase I (GTPCH). The aim of this study was to utilize adenoviral GTPCH gene transfer to reverse BH4 deficiency and repair the ability of endothelial cells to produce NO. GTPCH gene transfer increased BH4 levels in BBd endothelial cells from 0.17 +/- 0.02 (mean +/-SE) to 73.37 +/- 14.42 pmol/million cells and NO production from 0.77 +/- 0.07 to 18.74 +/- 5.52 nmol/24 h/million cells. To demonstrate a functional effect of increasing BH4 concentrations in tissues, we transferred GTPCH into aortic rings from BBd and Zucker diabetic fatty (ZDF) rats, models of human type I and type II diabetes, respectively. GTPCH gene transfer led to a dose-dependent increase in acetylcholine-induced vasorelaxation, preventable by inhibiting NO synthase. Maximal relaxation of virus-treated rings (10(10) virus particles/ml) to acetylcholine was significantly higher than sham-treated rings (BBd 64% vs. 37%, P

Summary Background Adherence is a major factor in determining disease activity in ulcerative colitis (UC). There are limited data on long-term nationwide adherence levels among patients with UC. Aim To evaluate the long-term adherence levels to oral mesalazine (mesalamine) in the Veterans Affairs (VA) healthcare system, to determine the impact of non-adherence on the risk of flares, and to evaluate the different pharmacy data-based adherence indicators. Methods Nationwide data were obtained from the VA for the period 2001–2011. UC patients who started mesalazine maintenance during the inclusion period were included. Level of adherence was assessed using three different indicators: medication possession ratio (MPR), continuous single-interval medication availability (CSA) and continuous multiple-interval medication gaps (CMG). Cox regression modelling was used to predict disease flares and assess the predictive value of each adherence indicator. Results We included 13 062 patients into the analysis with median follow-up time of 6.1 years. Percentage of patients with high adherence was 47%, 43%, 31% as identified by CSA, MPR and CMG respectively. Low adherers had a significant increase in the risk of flares compared with high adherers (Hazard ratio: 2.8, 1.7 and 1.8, P

Although frontal patients show impaired decision-making on the Iowa Gambling Task (IGT), there has been no follow-up study to date to determine whether there is recovery of function over time. We examined neurological participants’ performance on repeated administrations of the IGT over the course of 6 years. We found that, while non-neurological participants showed considerable improvement due to practice effects on the IGT, patients with ventromedial prefrontal cortex (VMPFC) damage persisted in showing impaired performance on each retest. These results validate the clinical observations that VMPFC dysfunction does not appear to be subject to autonomous recovery over time in real-life. (JINS, 2012, 18, 1–4)

MedlinePlus® is a premier consumer health portal. Developed by the National Library of Medicine in the late 1990s, this site added Go Local projects, beginning in 2003 with NC Health Info, to make information about facilities, providers, and services available at the local level. This article documents the literature about the Go Local programs.

The photoproduction of vector mesons on various nuclei has been studied using the Cebaf Large Acceptance Spectrometer (CLAS) at Jefferson Laboratory, and here we present preliminary results. All three vector mesons, ρ, ω, and ϕ, are observed via their decay to e+e-, in order to reduce the effects of final state interactions in the nucleus. Of particular interest is possible in-medium effects on the properties of the ρ meson. The ρ spectral function is extracted from the data on various nuclei, carbon, iron, and titanium, and compared to the spectrum from liquid deuterium, which is relatively free of nuclear effects. We observe no effects on the mass of the ρ meson, however, there is some widening of the resonance in titanium and iron, which is consistent with expected collisional broadening.

Aim An audit of the use of intravenous ketamine for the provision of conscious sedation in paediatric dentistry was carried out over a three-year period. Audit design In the audit, 3,751 children were treated and an evaluation was carried out for safety and effectiveness of the drug and procedure, the quality of sedation and clinical procedures provided. In addition, the occurrence of any adverse effects and parental satisfaction were noted along with recovery. All children were ASA I and II, with an average age of 7.5 years. Children were referred because of management problems and were assessed to be at the high anxious level of four and five on the Venham scale. A weight related 0.25 mg/kg was initially administered with additional increments of 0.25 mg/kg given if required. The average total dose provided was 0.41 mg/kg. Results The majority of children (76%) accepted all treatment with no problems, with 19% experiencing a small amount of resistance. Although a range of dental treatment was provided, it was mostly exodontias of carious primary dentition. A 27% response was provided assessing satisfaction which was very favourable. No adverse reactions occurred although the most common postoperative experience was nausea. Conclusion This audit demonstrated the safety and effectiveness of using intravenous ketamine for paediatric conscious sedation and implications for training and appropriate service delivery were discussed.

is a serious problem in spontaneous reporting schemes, with up to 94% of adverse drug reactions (ADRs) remaining unreported.[2] This study aims to investigate the views of GPs towards the YCS, identify potential blocks on reporting and motivating factors, and develop a theoretical framework to explain GPs’ involvement in the YCS. Method: A series (c.30) of qualitative interviews with GPs throughout the West Midlands, with purposive sampling of regular reporters, lapsed reporters and nonreporters were undertaken. Grounded theory was used to develop plausible relationships among developing concepts. N6 qualitative software (QSR International) was used to manage analysis of the interviews. MREC ethical approval was obtained. Results: Interviews conducted with lapsed and regular reporters shows that an increased administrative burden on GPs may be inhibiting reporting in some cases. A sense of duty and early educational knowledge of the scheme are important motivators. Individual reporters also developed their own personal criteria for reporting – including their own perceptions of plausibility. Many GPs had developed habits and mechanisms to remind themselves to report ADRs. Varying degrees of scepticism about the pharmaceutical industry were expressed, with the MHRA viewed as a counter-balance to the industry. Feedback to reporters from regulatory authorities was highly valued and this appears to be a motivator in continued reporting. Reminders of the continuing importance of the scheme were valued. Discussion: Many reporters to the YCS develop a sense of duty about reporting, in part caused by early exposure to the scheme during training. Reminders about the scheme’s importance and crucially feedback to reporters from the MHRA are important to maintaining reporting. The MHRA’s reputation is important, since reporting is seen as a public good to patients and other doctors. GP workload, particularly administrative parts, would appear to increasing, and some reporters cite this as a reason for reduced reporting rates. Conclusion: This study has identified several areas which motivate and inhibit reporting to the YCS. These factors should be considered in how the YCS is marketed and administered, as well as how wider changes in primary care may affect ADR reporting. Further quantitative research based on the findings of this study should be undertaken.

“Invariant object recognition” refers to the ability to recognize objects across variation in their appearance on the retina. This ability is central to visual perception, yet its developmental origins are poorly understood. Traditionally, nonhuman primates, rats, and pigeons have been the most commonly used animal models for studying invariant object recognition. Although these animals have many advantages as model systems, they are not well suited for studying the emergence of invariant object recognition in the newborn brain. Here, we argue that newly hatched chicks (Gallus gallus) are an ideal model system for studying the emergence of invariant object recognition. Using an automated controlled-rearing approach, we show that chicks can build a viewpoint-invariant representation of the first object they see in their life. This invariant representation can be built from highly impoverished visual input (three images of an object separated by 15° azimuth rotations) and cannot be accounted for by low-level retina-like or V1-like neuronal representations. These results indicate that newborn neural circuits begin building invariant object representations at the onset of vision and argue for an increased focus on chicks as an animal model for studying invariant object recognition.

It's a well-known fact that men are less likely than women to seek health care. Men tend to wait as long as possible to see a doctor about a health problem, making early diagnosis of a disease difficult if not impossible. When one looks at the statistics related to men's health, the apparent aversion to seeking health care is disconcerting. Given the fact that men seem to be more private about their illnesses, the Internet provides an excellent place for them to seek health care information. A search of "men's health" finds an overwhelming number of sites on the Internet. This article provides a highly selected list of Web sites intended as a starting place for finding information about men's health on the Internet.

Fresh and frozen ovaries from 10 day old C57BL/6J-Gpi-1(a) mice were grafted orthotopically into ovariectomized B6CBF1 (homozygous Gpi-1(b)) recipients. The recipients were mated with B6CBF1 males. The birth and size of each litter was recorded. The electrophoretic variant of glucose phosphate isomerase was determined for each neonate. Twelve of 13 recipients of fresh ovary and 10 of 12 recipients of frozen ovary were fertile. Of these, 10 (fresh) and eight (frozen) had litters derived from the ovarian grafts only, or from the graft and native ovary. The breeding characteristics of recipients of fresh and frozen grafts were similar. The reproductive lifespan of the recipients of fresh (6.2 litters) and frozen (8.4 litters) grafts was similar to that of unoperated C57BL/6-Gpi-1(a) control females mated with B6CBF1 males (6.3 litters). Litter size was similar in recipients of grafted ovaries (fresh, 5.4 pups/litter; frozen, 6.3 pups/litter) and C57BL/6-Gpi-1(a) females (6.3 pups/litter). The results suggest that cryopreservation per se does not affect the long-term viability of ovarian tissue and provides an option for storing female germ cells. This is the first unequivocal demonstration that a normal reproductive lifespan can be restored by orthotopic grafting of frozen ovary.

A prospective trial was carried out to assess the outcome of children aged from 2 to 6 weeks with stable but dysplastic hips, treated with abduction splintage or by observation. Forty-four patients with 63 dysplastic hips were entered into the study and allocated into the two treatment groups at random. The ultrasound measured percentage acetabular cover in the splinted group improved in the first 3 months from an average of 32.8 to 54.3%. In the unsplinted group, the increase in cover was from 36.7 to 48.6%. The changes in cover for the splinted group were significantly more than those for the unsplinted group (p < 0.003) There was, however, no significant difference between the two groups in acetabular angle measurements on plain radiographs taken at 3 months. At 24 months, similarly, there was no significant difference in the acetabular angles of the two groups. These results support the view that stable dysplastic hips will correct with growth and that there is no sustained benefit from early splintage.

Bacterial meningitis in adults (those aged over 15 years) is an uncommon but serious condition. The principles of prevention and treatment are easy to state but, unlike recommendations in guidelines for other conditions, the evidence base for many of our recommendations is lacking or a subject of controversy. The British Infection Society therefore convened a working party comprising clinicians, microbiologists, epidemiologists, general practitioner (GP) and Public Health representatives to assess current evidence and issue a clinically based consensus paper on the management of adult patients with suspected bacterial meningitis which would be useful for non-specialist physicians. The Working Party was aware that they had to make several recommendations using incomplete evidence. evidence from childhood meningitis, or from animal models. The grading of levels of evidence, adapted from AHCPR 1992 ’ . is given in Table I and the grading for our recommendations in Table II. We have included management of septicaemic presentations of meningococcal infection although such patients may not have meningitis. Adults with a meningitic presentation of meningococcal sepsis may have had a relatively mild bacteraemic phase and have a mortality rate of 5% or less whereas those who present with meningococcal septicaemia or sepsis unaccompanied by meningitis may have a mortality rate of 15-40% We have not included advice on management of meningitis following trauma or neurosurgery (except for recommendations for antibiotic treatment of pneumococcal meningitis).

A low-temperature cleaning technique incorporating an ultraviolet light–ozone treatment with conventional hydrogen-passivation techniques is shown to yield a low concentration of surface contaminants: 0.01 monolayer. An additional advantage is that no ultrahigh vacuum prebaking treatments are required for substrates receiving this treatment prior to epitaxy. Epitaxial silicon layers deposited onto substrates receiving the present technique are characterized by a threading dislocation density on the order of 104/cm2, which is considerably lower than the 105/cm2–106/cm2 order measured for films receiving more conventional preparation techniques. The results of this study suggest that aqueous solutions are a significant source of surface carbon and that residual carbon on the silicon surface before epitaxy contributes to the generation of threading dislocations in Si homoepitaxial films.

Ovaries from 10-day-old mice were exposed to 1.5 mol l-1 dimethylsulfoxide, 1,2-propanediol, ethanediol or glycerol for 5-60 min at room temperature before freezing. Follicles in fresh and frozen ovaries were counted and scored as normal or damaged in stained serial sections. More primordial follicles survived in ovaries frozen in dimethylsulfoxide, 1,2-propanediol and ethanediol (81-94%) than in those frozen in glycerol (4-28%). Prolonged exposure to ethanediol (60 min) before cooling decreased the survival rate, while increasing the exposure to glycerol (> or = 12 min) increased the survival rate. Fewer than 49% of primary follicles survived freezing. After transfer underneath the kidney capsules of ovariectomized immunodeficient recipients, there was no difference in the establishment of grafts of fresh (92%) and frozen (90%) ovaries, the number of recipients showing vaginal cornification (fresh, 91%, frozen 96%) or the latency of cornification (11 days). Fifteen days after transplantation, similar numbers of follicles remained in grafts of fresh ovaries, in ovaries frozen in dimethylsulfoxide and 1,2-propanediol, and in ovaries frozen after exposure to ethanediol for 5-30 min. Overall, the total number of follicles remaining in grafts of ovaries frozen in dimethylsulfoxide and 1,2-propanediol represented 42-46% of follicles present in ungrafted ovaries. This was not significantly different from grafts of fresh ovaries (63%). Dimethylsulfoxide and 1,2-propanediol are the most effective cryoprotectants for 10-day-old mouse ovaries. The majority of follicles are lost during graft establishment.

In a previous study we examined whether frontal patients with impaired decision-making on the Iowa Gambling Task (IGT) would recover over time if retested on the IGT. However, a major limitation of repeated administration of the IGT is practice effects, where control participants show improvement with retesting (Bechara, Damasio, & Damasio, 2000). Therefore, the primary goal of this study was to design two alternative versions of the IGT to eliminate practice effects. We found that control participants did not show improvement in performance across the different versions of the task, thus reflecting success in our attempt to design alternative versions of the IGT. Compared to control participants, patients with damage to the ventromedial prefrontal cortex (vmPFC) performed worse on all three versions of the IGT, even after controlling for age, sex, and education. The development of alternative versions of the IGT provides a valuable tool for clinicians and researchers to utilize the IGT as a way to track how the decision-making abilities of patients change over time. Additionally, these results are consistent with findings from the original studies using the IGT with patients with damage to the vmPFC which showed that decision-making impairments do not recover over time.

Antiviral drugs, other than those with anti-retroviral activity, are used in persons with human immunodeficiency virus (HIV) infection for two purposes : treatment or prevention of viral infections that cause disease in persons with immunodeficiency, and to suppress viruses that might act as co-factors and promote replication of HIV itself. Human herpesviruses are the major targets of therapy in both settings. The herpesviruses, particularly cytomegalovirus (CMV), herpes simplex virus (HSV) and varicella-zoster virus (VZV) act as opportunistic pathogens as cell-mediated immunity declines, and there is theorectical, in-vitro, and in-vivo evidence that one or more herpesviruses can accelerate the progression of HIV disease. Therapy and prophylaxis with antiherpes compounds such as acyclovir, ganciclovir and foscarnet are well established in HIV infection, and this article will review their present use and recent improvements in formulations and drug delivery.

Section I: Introduction/Overview 1. Overview of Health Sciences Libraries and Librarianship Mary Moore 2. The Health Care Environment Logan Ludwig Appendix 2. A. Selected Federal Legislation with Important Health Aspects, Including Health Care Information Policy Legislation Section II: Technical Services 3. Journal Collection Development: Challenges, Issues, and Strategies Laurie L. Thompson, Mori Lou Higa 4. Monographic and Digital Resource Collection Development Esther Carrigan, Mori Lou Higa, Rajia Tobia 5. Organizing Resources for Information Access Maggie Wineburgh-Freed Appendix 5. A. Resource Bibliography for Organizing Information Section III: Public Services 6. Access Issues, Elizabeth R. Lorbeer, Cindy Scroggins 7. Information Services in Health Sciences Libraries Elizabeth H. Wood 8. Information Retrieval in the Health Sciences Elizabeth H. Wood 9. Marketing, Public Relations, and Communication Patricia C. Higginbottom, Lisa A. Ennis Appendix 9. A. Additional Readings 10. Information Literacy Education in Health Sciences Libraries Stewart M. Brower 11. Evidence-Based Practice Jonathan D. Eldredge 12. Health Informatics K. Ann McKibbon, Ellen Gay Detlefsen Section IV: Administration 13. Management in Academic Health Sciences Libraries Francesca Allegri, Martha Bedard 14. Management of and Issues Specific to Hospital Libraries Dixie A. Jones 15. Library Space Planning Elizabeth Connor Section V: Special Topics 16. Special Services Provided by Health Sciences Libraries Brenda L. Seago 17. Health Sciences Librarianship in Rare Book and Special Collections Stephen J. Greenberg, Patricia E. Gallagher 18. Consumer Health Information Catherine Arnott Smith Glossary Index

The shelf-life of vancomycin in infusion fluids was studied using high-performance liquid chromatographic (HPLC) methods. Vancomycin was stable (loss in potency less than 10%) for 47 days and 29 days, respectively, when dissolved in water-for-injections BP at 25 degrees C and stored in plastic syringes (Becton Dickinson Plastipak (three-piece) and B. Braun Medical Injekt (two-piece)). In sodium chloride solution (0.9%; pH 5.4) it was stable for 62 and 34 days, while in dextrose solution (5%; pH 4.2) it was stable for 55 and 33 days, respectively, at the same temperature. At 4 degrees C vancomycin was stable in all three infusion fluids and both types of syringe for at least 84 days.

Mature mouse oocytes were cryopreserved by vitrification in 6 M dimethyl sulfoxide (VS). After warming they were either artificially activated with strontium (Sr 2+ ), and the incidence of chromosome non-disjunction was assessed at first cleavage metaphase ; or they were fertilized in vitro, and postimplantation survival was examined at Day 15 of gestation. Similar proportions of vitrified and freshly collected oocytes were activated with Sr 2+ (75% and 82%, respectively). The majority of activated oocytes extruded the second polar body and formed a single pronucleus (> 90%). When the exposure time to VS was increased from 90 to 110 see without cooling, a significant proportion of activated oocytes arrested at the pronuclear stage (30%), and chromosome condensation did not occur. The frequency of aneuploidy in vitrified and control oocytes was similar, but when exposure to VS without cooling was extended, aneuploidy and second polar body retention were significantly higher than those of controls (p < 0.05). The rates of fertilization of vitrified (85%) and control oocytes (92%) did not differ. After transfer, similar proportions of vitrified and control embryos implanted (68-80%) and formed normal fetuses (38-49%). We conclude that vitrification in 6 M dimethyl sulfoxide is a simple and safe procedure for the preservation of mouse oocytes provided that the time of exposure to the cryoprotectant is carefully controlled.

Pieces of marmoset ovary were frozen by slow cooling in 1.5 M dimethylsulphoxide. The follicles in fresh and frozen tissue were counted and examined for morphological appearance in stained serial sections. The proportion of normal follicles was similar in fresh tissue and frozen tissue examined immediately after thawing. Follicles at all stages of folliculogenesis up to the small antral stage survived freezing and thawing. Fresh and frozen tissue was transplanted underneath the kidney capsules of ovariectomized immunodeficient mice. The establishment of grafts was similar, and oestrogenic activity (cornification of the vaginal epithelium) was observed in the recipients 20 and 16 days after transplantation of fresh and frozen grafts respectively. The total number of follicles and the proportion of normal follicles were similar in fresh and frozen grafts. Grafts of frozen tissue recovered between 7 and 15 days after transfer contained follicles up to the small antral stage of development. Grafts recovered between 21 and 32 days contained follicles at all stages of folliculogenesis, including large antral follicles (1-2 mm diameter). Our results suggest that freezing and thawing do not substantially damage marmoset ovarian tissue, and the cryopreserved tissue retains its ability to support the development of large antral follicles.

A retrospective evaluation of the functional results after reconstructive treatment with levator scapulae transfer and scapulo-spinal fasciodesis by fascia lata slings for complete chronic trapezius palsy is presented. Five patients (ages 6 to 40 years) were operated on between 1988 and 1991 because of incapacitating pain and/or functional limitations. Treatment was recommended after failure to alleviate symptoms by a shoulder-girdle muscle-strengthening program or after unsuccessful nerve graft. The descriptions of the results are drawn from the last follow-up evaluation available for each patient (minimum: 14 months post-operative). They are expressed in terms of functional recovery, residual pain, and patient satisfaction. Three patients had an excellent result, with at least 80 percent of normal abduction and forward elevation of the arm, no residual pain, and a high satisfaction rate. One patient showed good improvement in function, with 90 percent of normal shoulder function, but complained of some residual pain. The last patient was not improved by the surgery. Levator scapulae transfer and scapulo-spinal fasciodesis by fascia lata slings, substitute for the function of the upper trapezius and enhance the function of the serratus anterior, thus helping to relieve pain and to improve shoulder function after chronic trapezius palsy. The procedure warrants consideration in patients who are not candidates for nerve repair and reconstruction.

Acyclovir treatment of acute herpes zoster speeds rash healing and decreases pain and ocular complications. The limited oral bioavailability of acyclovir necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, is rapidly and almost completely converted to acyclovir in vivo and gives three- to fivefold increases in acyclovir bioavailability. In a randomized, double-blind, multicenter study, the safety and efficacy of oral valaciclovir given at a dosage of 1,000 mg three times daily for 7 or 14 days and oral acyclovir given at a dosage of 800 mg five times daily for 7 days were compared in immunocompetent adults aged > or = 50 years with herpes zoster. Patients were evaluated for 6 months. The intent-to-treat analysis (1,141 patients) showed that valaciclovir for 7 or 14 days significantly accelerated the resolution of herpes zoster-associated pain (P = 0.001 and P = 0.03, respectively) compared with acyclovir; median pain durations were 38 and 44 days, respectively, versus 51 days for acyclovir. Treatment with valaciclovir also significantly reduced the duration of postherpetic neuralgia and decreased the proportion of patients with pain persisting for 6 months (19.3 versus 25.7%). However, there were no differences between treatments in pain intensity or quality-of-life measures. Cutaneous manifestations resolved at similar rates in all groups. Adverse events were similar in nature and prevalence among groups, and no clinically important changes occurred in hematology or clinical chemistry parameters. Thus, in the management of immunocompetent patients > or = 50 years of age with localized herpes zoster, valaciclovir given at 1,000 mg three times daily for 7 days accelerates the resolution of pain and offers simpler dosing, while it maintains the favorable safety profile of acyclovir.

Since the discovery of short interfering RNAs (siRNAs), their potential as a therapeutic platform has been widely recognized. However, clinical translation has been stalled by inefficient delivery in vivo. While some success has been achieved with cationic lipids and lipid-like materials for therapeutic RNAi delivery to liver, delivery across the blood–brain barrier (BBB) to the central nervous system for the treatment of neurological disorders such as Parkinson’s, Alzheimer’s, and Huntington’s disease remains a challenge. To address the problem of inefficient delivery across the BBB, our laboratory exploited one of nature’s mechanisms for intercellular communication, named exosomes. They are a class of membrane vesicles derived from the endolysosomal compartment implicated in cell–cell communication by shuttling various proteins, lipids, and RNAs between cells. We have developed a method to target exosomes with brain-specific peptides and subsequently load them with siRNA for targeted delivery to brain. This chapter aims at providing an insight into membrane vesicle-mediated RNA delivery and how these vectors can be utilized for RNAi therapy.

The properties of hadrons, such as their masses and widths, are predicted to be modified in dense and/or hot nuclear matter. Particular attention has been given to the modifications of vector-meson properties in ordinary nuclear matter where chiral symmetry is predicted to be partially restored due to a change in the quark condensate. Different models predict relatively large measurable changes in the mass and/or the width of these mesons. The e+e− decay channel of these mesons has negligible final-state interactions (FSI), providing an ideal tool to study their possible in-medium modifications Due to its short lifetime, the ρ meson has a substantial probability of decaying in the nucleus and its study has been previously reported. Due to their long lifetimes, the ω and φ mesons are ideal candidates for the study of possible modifications of the in-medium meson-nucleon interaction through their absorption inside the nucleus. These mesons have been photo-produced in several targets ranging from deuterium t...

Mouse oocytes enclosed in cumulus cells were isolated from antral follicles at the germinal vesicle (GV) stage. They were stored in straws at -196 degrees C by a conventional mouse embryo freezing method using dimethylsulphoxide (1.5 M) as the cryoprotectant. Overall survival assessed after removal of the cumulus cells was 93% (299/320). A significantly greater proportion of fresh oocytes remained arrested at the GV stage during culture (11 versus 1%), but the rate of maturation to metaphase II was not significantly different between frozen and fresh oocytes (83 versus 74%). The rate of fertilization in vitro was similar for frozen and fresh oocytes matured in vitro (70 versus 81%) but significantly less than with mature ovulated oocytes (96%). Fertilization of frozen and fresh oocytes arrested after germinal vesicle breakdown was similar (77 versus 95%). No evidence of parthenogenetic activation was found in the different groups after overnight incubation of metaphase II oocytes. Implantation was similar for embryos derived from fresh and frozen GV-stage oocytes matured in vitro and mature ovulated oocytes, but the loss of embryos after implantation was significantly higher in the in-vitro matured groups (frozen, 40% and fresh, 46% versus 24%). The overall survival of oocytes frozen at the GV stage was 27%. This compares favourably with the estimated overall survival of mature oocytes cryopreserved by a similar procedure. We conclude that the increased post-implantation loss is due to suboptimal conditions for maturation in vitro rather than freezing injury.

A high proportion (> 70%) of mouse and hamster oocytes exposed for 3-5 min to 1.5 M dimethylsulfoxide (DMSO) and washed briefly in 3.9 M DMSO before vitrification in 6.0 M DMSO appeared morphologically normal on recovery. Significantly fewer ( 90% ) or human (21% vs. 23% ) sperm. Sperm nuclear decondensation and pronuclear formation appeared to be delayed in the cytoplasm of vitrified hamster oocytes. Seventy-nine percent of 2-cell-stage mouse embryos derived from vitrified oocytes implanted after transfer to pseudopregnant recipients, but only 40% developed to normal fetuses compared to 61% of controls. The reason for this high rate of postimplantation loss is unknown.

The interaction of the enantiomers of mianserin with the 5-HT3 receptor was determined. Using [3H]granisetron binding, (–)-mianserin was more potent than (+)-mianserin (pKi 8·46 and 6·95, respectively). The enantiomers competitively antagonized the depolarizing effect of 5-hydroxytryptamine in the rat vagus nerve preparation (pKapp: (–)-mianserin 8·13, (+)-mianserin 6·58). This stereoselectivity was maintained in-vivo as determined using ex-vivo inhibition of [3H]granisetron binding. Therefore, in contrast to its enantiomeric selectivity for the 5-HT1C and 5-HT2 receptors, where the (+)-isomer is more potent, the enantiomeric selectivity of mianserin for the 5-HT3 receptor was reversed. This differential selectivity of the enantiomers of mianserin may be useful in elucidating its utility in anxiety states.

Freezing and thawing of mouse oocytes causes changes in the zona pellucida that reduce fertilization. The fertilization and development of oocytes were studied after freezing and thawing in media containing 1.5 M dimethylsulfoxide (DMSO) and various macromolecular supplements: BSA (Fraction V and crystalline), fetal calf serum (FCS), and polyvinyl alcohol (PVA). In conditions under which the fertilization rate of oocytes frozen in medium containing BSA was reduced, oocytes frozen in medium containing FCS were fertilized at rates approaching those of nonfrozen controls. Significantly fewer oocytes were fertilized after freezing in the presence of PVA than oocytes frozen in medium containing BSA or FCS. Fertilization of oocytes frozen in the presence of PVA was significantly increased when serum was included in the medium during dilution of the cryoprotectant. The in vitro and in vivo development of embryos obtained from frozen-thawed oocytes was independent of the macromolecular supplement used in the freezing medium and was similar to that of nonfrozen control oocytes. The results show that given the appropriate conditions for freezing and thawing, cryopreserved mouse oocytes undergo fertilization and development at rates similar to those for nonfrozen controls.

882C87 [1-(beta-D-arabinofuranosyl)-5-propynyluracil] is a nucleoside analogue with potent and specific antiviral activity against varicella-zoster virus (VZV). The IC50 of 882C87 against VZV ranges from 0.6 to 3.8 microM. Potentially therapeutic plasma concentrations are readily achieved in humans; the pharmacokinetics have been previously evaluated in healthy young and elderly (65 years) volunteers following single oral doses of 50-400 mg. Thirty immunocompetent patients with localised herpes zoster were treated with 882C87. Groups of patients received 50 mg, 100 mg, or 200 mg tablets of 882C87 every 12 hours for 7 or 7.5 days (14 or 15 doses). Six patients in each group were over 60 years of age. Blood samples for determination of 882C87 concentrations were taken at entry, steady state, and during the elimination phase following the last dose. After the final doses of the 50 mg 100 mg, and 200 mg dosage regimens, the Cmax of 882C87 in patients over 60 years old was 7.7 +/- 3.1 microM, 12.6 +/- 3.5 microM, and 24.8 +/- 14.0 microM, respectively, and the AUCs 0-12 were 78.4 +/- 31.8 microM.hr, 137.5 +/- 22.8 microM.hr, and 272.5 +/- 170.5 microM.hr, respectively. Preliminary estimates of the elimination half-life ranged from 15.1 to 20.0 hr. These preliminary pharmacokinetic data confirmed good dose proportionality for AUC and Cmax with values between those predicted from single dose data in the young and those in elderly volunteers. The plasma concentration profiles at these doses were in excess of IC50 values and support the use of once- or twice-daily regimens in future studies of 882C87 in herpes zoster.

We hypothesized that exemestane (EXE) would reduce mammographic breast density and have unique effects on biomarkers of bone and lipid metabolism. Healthy postmenopausal women were randomized to EXE (25 mg daily) or placebo (PLAC) for 12 months and followed for a total of 24 months. The primary endpoint was change in percent breast density (PD) between the baseline and 12-month mammograms and secondary endpoints were changes in serum lipid levels, bone biomarkers, and bone mineral density (BMD). Ninety-eight women were randomized (49 to EXE; 49 to PLAC) and 65 had PD data at baseline and 12 months. Among women treated with EXE, PD was not significantly changed from baseline at 6, 12, or 24 months and was not different from PLAC. EXE was associated with significant percentage increase from baseline in N-telopeptide at 12 months compared with PLAC. No differences in percent change from baseline in BMD (lumbar spine and femoral neck) were observed between EXE and PLAC at either 12 or 24 months. Patients on EXE had a significantly larger percent decrease in total cholesterol than in the PLAC arm at 6 months and in HDL cholesterol at 3, 6, and 12 months. No significant differences in percent change in LDL or triglycerides were noted at any time point between the two treatment arms. EXE administered for 1 year to healthy postmenopausal women did not result in significant changes in mammographic density. A reversible increase in the bone resorption marker N-telopeptide without significant change in bone specific alkaline phosphatase or BMD during the 12 months treatment period and 1 year later was noted. Changes in lipid parameters on this trial were modest and reversible.

Chlamydia psittaci is the major cause of infectious disease in the koala (Phascolarctos cinereus). It causes four disease syndromes in the koala, namely, conjunctivitis, rhinitis, cystitis, and infertility (females only). Diagnosis of chlamydial infections in koalas relies primarily on isolation of the organism in cell culture. Serology has generally not been useful, and little use has previously been made of the commercially available antigen detection kits. We examined the sensitivity, specificity, and usefulness of three direct fluorescent-antibody kits (Vet-IF [Cell Labs], IMAGEN [Celltech], Chlamydia-Direct IF [Bio Merieux]) and six antigen detection enzyme-linked immunosorbent assay (ELISA) kits (Clearview [Unipath], Surecell [Kodak], Pathfinder [Kallestad], Chlamydia-EIA [Pharmacia], Chlamydiazyme [Abbott], IDEIA [Celltech]) for the detection of urogenital infections in koalas. Laboratory studies showed that the direct fluorescent-antibody kits were the least sensitive in this case and did not detect fewer than 10(4) elementary bodies per ml, while most ELISA kits detected between 130 and 600 elementary bodies per ml. Field study results showed that the Clearview kit was the most sensitive (91%) compared with the IDEIA (88%) and the Surecell (73%) kits. All three kits were more sensitive than cell culture (36%), highlighting viability loss problems that occur during transport. This study showed that the Clearview kit is sensitive, specific, and easy to use for the detection of type II (urogenital) C. psittaci from koalas in the field and warrants further evaluation.