NeuroPharmacology: As Applied to Designing New Chemotherapeutic Agents

Neurooncology anticancer drugs are no exception—their distribution and tissue interactions follow the general rules of classical pharmacology. In an attempt to assist with the new therapeutic approaches to manage cancers involving the central nervous system, classical chemobiodynamic compartment and pharmacokinetic models are discussed and illustrated. In addition, strategies and approaches for penetrating the blood brain barrier (BBB) are reviewed and modeled. Finally, in support of classical pharmacology, a new anticancer agent in clinical trial for brain tumors is reviewed as an example of clinical onco-neuropharmacology

Patient Perspectives of the Doctor-at-Home Service

Introduction. Home health care has been established as an effective model for reducing mortality in the elderly. The Doctor-at-Home Service at the Community Health Centers of Burlington (CHCB) has offered home health care to Burlington residents since January 2015. Dr. Karen Sokol, MD, alone provides care to 176 patients at their homes, including at-home palliative care. CHCB hope to expand this program by hiring more providers. Objective. To understand the impact of the Doctor-at-Home Service from the pa- tients’ perspective. Methods. A survey was administered to a cohort of eighteen patients over an 8- week period and addressed topics such as barriers to healthcare, benefits, and costs associated with doctor-at-home programs. A theme analysis on the responses was then conducted to reflect patient opinions. Available summary data describing the pa- tient population was also analyzed. Results. The Doctor- at- Home program serves patients ranging from 26 to 100 years old, with the majority of the patient population comprised of senior citizens. Prior to at home care, patients faced barriers such as lack of transportation, negative past experi- ences, anxiety, and distance from relatives. Four main themes from patient responses were physician-patient relationship, convenience, quality of care, and environment of care. Discussion. Evidence is compelling that there is a desire and need for an exten- sion of the Doctor-at-Home program to reach additional patients. Doctor-at-Home pro- grams could eliminate identified barriers and provide quality care to patients, especially those with specific barriers to access.https://scholarworks.uvm.edu/comphp_gallery/1256/thumbnail.jp

A rate-based approach to cleaning-in-place

Fouling is a major problem in the food industry. In cases where allergens are involved, excessive cleaning of food processing equipment often takes place to ensure allergen levels are reduced to acceptable levels. Experimental trials were conducted in a pilot scale cleaning rig to assess the effect of fluid flow rate and temperature on the removal rate of milk paste during cleaning-in-place. Conductivity measurements taken during trials were analysed to produce an equation enabling calculation of the cleaning rate with water temperature, flow rate, initial deposit mass, and time. The rate of cleaning with detergent was also investigated. This methodology produces a rate based expression for cleaning which can be applied to other products, and can be used to determine the time when cleaning is complete, the extent of a cleaning process, or when the pre-rinse should be replaced with a detergent rinse. This prevents over-cleaning and therefore reduces the costs associated with over-cleaning through energy, material and loss of production time

Estudio de estrategias financiera para la empresa Total Marcas SAS

Trabajo de síntesisEl propósito de este trabajo de síntesis aplicada se basa en la realización de un análisis financiero de la sociedad por acciones simplificada TOTAL MARCAS S.A.S. con el fin de conocer el estado real de la compañía y así generar un documento que permita el estudio y posible aplicación de estrategias financieras para la sociedad antes mencionada o cualquier otra compañía de similares características que le permitan tener una eficiente administración de recursos financieros.1. INTRODUCCION 2. ESTADO ACTUAL EMPRESA 3. COMPARATIVO FRENTE AL SECTOR 4. INDICADORES PROPUESTOS 5. ESTRATEGIAS FINANCIERAS BIBLIOGRAFÍAEspecializaciónEspecialista en Análisis y Administración Financier

Comparative Anticancer Activity in Human Tumor Xenograft Models, Preclinical Pharmacology and Toxicology for 4- Hydroperoxyifosfamide (HOOI): A Potential Neuro-Alkylating Agent for Primary and Metastatic Cancers Involving the Central Nervous System

Background: 4-Hydropeoxyifosfamide (HOOI) is a hydroperoxy derivative of ifosfamide that was developed as an anticancer agent that can penetrate the blood-brain barrier (BBB), which can be potentially useful in the management of brain tumors

Association between first-year virological response to raltegravir and long-term outcomes in treatment-experienced patients with HIV-1 infection

Background: We explored the relationship between virological response in the first year of treatment and long-term outcomes in the BENCHMRK studies. Methods: Patients failing antiretroviral treatment with 3-class resistant HIV-1 received double-blinded raltegravir (or placebo) with optimized background therapy (OBT) until week 156, followed by open-label raltegravir with OBT up to week 240. In this exploratory analysis of patients randomized to raltegravir, virological response over weeks 16-48 was categorized as continuous suppression (CS; viral RNA [vRNA] always 50 copies/ml at least once), or not suppressed (NS; vRNA >400 copies/ml at least once). The association between these first-year vRNA response categories and baseline factors was analysed with univariate and multivariate models. Virological and immunological outcomes for years 2-5 were assessed by first-year vRNA response category (observed failure approach). Results: Baseline vRNA, baseline CD4(+) T-cell count and rapid viral decay (vRNA <50 copies/ml between weeks 2-12) correlated with first-year vRNA response (P<0.001); only rapid viral decay remained significant by multiple regression. Virological response rates were similar in the LLV and CS groups and lowest in the NS group. CD4(+) T-cell count increased through week 240 in the CS and LLV groups. Time to loss of virological response (confirmed vRNA ≥400 copies/ml) through week 240 did not support as strong a difference between the LLV and CS groups (log-rank P=0.11) as previously reported through weeks 156 and 192 (P<0.05). Conclusions: Treatment-experienced patients on a raltegravir-based regimen with early LLV may have long-term virological and immunological benefit when their therapy is maintained

Electroencephalographic field influence on calcium momentum waves

Macroscopic EEG fields can be an explicit top-down neocortical mechanism that directly drives bottom-up processes that describe memory, attention, and other neuronal processes. The top-down mechanism considered are macrocolumnar EEG firings in neocortex, as described by a statistical mechanics of neocortical interactions (SMNI), developed as a magnetic vector potential $\mathbf{A}$. The bottom-up process considered are $\mathrm{Ca}^{2+}$ waves prominent in synaptic and extracellular processes that are considered to greatly influence neuronal firings. Here, the complimentary effects are considered, i.e., the influence of $\mathbf{A}$ on $\mathrm{Ca}^{2+}$ momentum, $\mathbf{p}$. The canonical momentum of a charged particle in an electromagnetic field, $\mathbf{\Pi} = \mathbf{p} + q \mathbf{A}$ (SI units), is calculated, where the charge of $\mathrm{Ca}^{2+}$ is $q = - 2 e$, $e$ is the magnitude of the charge of an electron. Calculations demonstrate that macroscopic EEG $\mathbf{A}$ can be quite influential on the momentum $\mathbf{p}$ of $\mathrm{Ca}^{2+}$ ions, in both classical and quantum mechanics. Molecular scales of $\mathrm{Ca}^{2+}$ wave dynamics are coupled with $\mathbf{A}$ fields developed at macroscopic regional scales measured by coherent neuronal firing activity measured by scalp EEG. The project has three main aspects: fitting $\mathbf{A}$ models to EEG data as reported here, building tripartite models to develop $\mathbf{A}$ models, and studying long coherence times of $\mathrm{Ca}^{2+}$ waves in the presence of $\mathbf{A}$ due to coherent neuronal firings measured by scalp EEG. The SMNI model supports a mechanism wherein the $\mathbf{p} + q \mathbf{A}$ interaction at tripartite synapses, via a dynamic centering mechanism (DCM) to control background synaptic activity, acts to maintain short-term memory (STM) during states of selective attention.Comment: Final draft. http://ingber.com/smni14_eeg_ca.pdf may be updated more frequentl

Morphometric and gene expression analyses of stromal expansion during development of the bovine fetal ovary

During ovarian development stroma from the mesonephros penetrates and expands into the ovarian primordium and thus appears to be involved, at least physically, in the formation of ovigerous cords, follicles and surface epithelium. Cortical stromal development during gestation in bovine fetal ovaries (n = 27) was characterised by immunohistochemistry and by mRNA analyses. Stroma was identified by immunostaining of stromal matrix collagen type I and proliferating cells were identified by Ki67 expression. The cortical and medullar volume expanded across gestation, with the rate of cortical expansion slowing over time. During gestation, the proportion of stroma in the cortex and total volume in the cortex significantly increased (P  0.05). The expression levels of 12 genes out of 18 examined, including osteoglycin (OGN) and lumican (LUM), were significantly increased later in development (P < 0.05) and the expression of many genes was positively correlated with other genes and with gestational age. Thus, the rate of cortical stromal expansion peaked in early gestation due to cell proliferation, whilst late in development expression of extracellular matrix genes increased.M.D. Hartanti, A K. Hummitzsch, H.F. Irving-Rodgers, W.M. Bonner, K.J. Copping, R.A. Anderson, I.C. McMillen, V.E.A. Perry and R.J. Rodger

Public involvement in health and social sciences research: A concept analysis.

BACKGROUND: Research funding bodies have significantly increased emphasis on the need for public involvement in research with the requirement to evidence effective methods and approaches to achieving this. Specific definitions and approaches within published research remain tokenistic and vague. OBJECTIVE: The concept analysis explores and clarifies the nature and meaning of public involvement in health and social sciences research and identifies operational definitions which can be used to guide, develop and evaluate public involvement in research activity. SEARCH STRATEGY: A literature search was conducted using online databases. Systematic literature reviews and broader studies on the impact of PPI were included as was grey literature such as guidance from INVOLVE and research funding bodies. Limits were set to papers published in the last 10 years and in the English language. A concept analysis framework adapted from Rodgers (Concept Development in Nursing: Foundations, Techniques and Applications. London, UK: Saunders; 2000) and Walker and Avant (Strategies for Theory construction in Nursing. Boston, MA: Pearson Prentice Hall; 2005) was applied. MAIN RESULTS: Five operational definitions were developed from the concept analysis: undefined involvement; targeted consultation; embedded consultation; co-production; and user-led research. Typical examples of each approach were identified from the literature. Defining attributes included having clear and agreed meaning and purpose for any involvement; reciprocal relationships; and value and recognition of the expertise of all those involved. CONCLUSIONS: The authors argue the need for researchers to more explicitly incorporate and evaluate details of approaches used. Impact of public involvement on a research study should be identified when reporting on findings to prevent tokenistic practices where involvement is viewed as secondary to the core research process