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Experimental Biology and Medicine... Apr 2017The ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of... (Review)
Review
The ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of the various physiological mechanisms that are active during volume loss and that have the ability to stave off hemodynamic collapse. This review provides new insights about the physiology that underlies blood loss and shock in humans through the development of a simulated model of hemorrhage using lower body negative pressure. In this review, we present controlled experimental results through utilization of the lower body negative pressure human hemorrhage model that provide novel insights on the integration of physiological mechanisms critical to the compensation for volume loss. We provide data obtained from more than 250 human experiments to classify human subjects into two distinct groups: those who have a high tolerance and can compensate well for reduced central blood volume (e.g. hemorrhage) and those with low tolerance with poor capacity to compensate.We include the conceptual introduction of arterial pressure and cerebral blood flow oscillations, reflex-mediated autonomic and neuroendocrine responses, and respiration that function to protect adequate tissue oxygenation through adjustments in cardiac output and peripheral vascular resistance. Finally, unique time course data are presented that describe mechanistic events associated with the rapid onset of hemodynamic failure (i.e. decompensatory shock). Impact Statement Hemorrhage is the leading cause of death in both civilian and military trauma. The work submitted in this review is important because it advances the understanding of mechanisms that contribute to the total integrated physiological compensations for inadequate tissue oxygenation (i.e. shock) that arise from hemorrhage. Unlike an animal model, we introduce the utilization of lower body negative pressure as a noninvasive model that allows for the study of progressive reductions in central blood volume similar to those reported during actual hemorrhage in conscious humans to the onset of hemodynamic decompensation (i.e. early phase of decompensatory shock), and is repeatable in the same subject. Understanding the fundamental underlying physiology of human hemorrhage helps to test paradigms of critical care medicine, and identify and develop novel clinical practices and technologies for advanced diagnostics and therapeutics in patients with life-threatening blood loss.
Topics: Arterial Pressure; Blood Volume; Hemodynamics; Humans; Models, Cardiovascular; Oxygen; Shock, Hemorrhagic
PubMed: 28346013
DOI: 10.1177/1535370217694099 -
Journal of Clinical Oncology : Official... Mar 2013Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced... (Review)
Review
Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non-small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non-cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Humans; Lung Neoplasms; Maintenance Chemotherapy; Meta-Analysis as Topic; Quality of Life
PubMed: 23401441
DOI: 10.1200/JCO.2012.43.7459 -
Kidney Medicine 2020People with end-stage kidney disease receiving peritoneal dialysis (PD) are generally physically inactive and frail. Exercise studies in PD are scarce and currently...
BACKGROUND
People with end-stage kidney disease receiving peritoneal dialysis (PD) are generally physically inactive and frail. Exercise studies in PD are scarce and currently there are no PD exercise programs in the United States. The primary objective of this study was to test the feasibility of a combined resistance and cardiovascular exercise program for PD patients under the care of a dedicated home dialysis center in the United States.
STUDY DESIGN
Parallel randomized controlled feasibility study.
SETTING & PARTICIPANTS
PD patients were recruited from a single center and randomly assigned to the intervention (exercise; n = 18) or control (nonexercise; n = 18) group.
INTERVENTION
The intervention group received monthly exercise physiologist consultation, exercise prescription (resistance and aerobic exercise program using exercise bands), and 4 exercise support telephone calls over 12 weeks. The control group received standard care.
OUTCOMES
The primary outcome was study feasibility as measured by eligibility rates, recruitment rates, retention rates, adherence rates, adverse events, and sustained exercise rates. Secondary outcome measures were changes in physical function (sit-to-stand test, timed-up-and-go test, and pinch-strength tests) and patient-reported outcome measures.
RESULTS
From a single center with 75 PD patients, 57 (76%) were deemed eligible, resulting in a recruitment rate of 36 (63%) patients. Participants were randomly assigned into 2 groups of 18 (1:1). 10 patients discontinued the study (5 in each arm), resulting in 26 (72%) patients, 13 in each arm, completing the study. 10 of 13 (77%) intervention patients were adherent to the exercise program. A test analysis of covariance found a difference between the treatment groups for the timed-up-and-go test ( = 0.04) and appetite ( = 0.04). No serious adverse events caused by the exercise program were reported.
LIMITATIONS
Single center, no blinded assessors.
CONCLUSIONS
A resistance and cardiovascular exercise program appears feasible and safe for PD patients. We recommend that providers of PD therapy consider including exercise programs coordinated by exercise professionals to reduce the physical deterioration of PD patients.
FUNDING
None.
TRIAL REGISTRATION
NCT03980795.
PubMed: 32734246
DOI: 10.1016/j.xkme.2020.01.005 -
Water Research Aug 2022The increasing environmental problems due to various organic micropollutants in water cause the search of suitable additional water treatment methods. Gaining...
The increasing environmental problems due to various organic micropollutants in water cause the search of suitable additional water treatment methods. Gaining experimental data for the large amount and variety of pollutants would consume a lot of time as well as economic and ecologic resources. An alternative approach is predictive quantitative structure-property relationship (QSPR) modeling, which establishes a correlation between the structural properties of a molecules with a biological, physical, or chemical property. Therefore, in this study, QSPR modeling has been conducted using extensive validation techniques and statistical test to investigate the structural influence on the degradability of organic micropollutants with ozonation. In contrast to most of the other studies, the underlying dataset - rate constants for 92 organic molecules - were obtained under standardized conditions with defined experimental parameters. QSPR modeling was executed using a combination of the software PaDEL for descriptor calculation and QSARINS for the modeling process respecting all five OECD-requirements for applicable QSAR/QSPR-models. The final model was selected using a multi-criteria decision-making tool to evaluate the model quality based on all calculated statistical quality parameters. The model included 10 selected descriptors and fingerprints and showed good regression abilities, predictive power, and stability (R² = 0.8221, CCC = 0.9024, Q² = 0.7436, R² = 0.8420, Q² = 0.8104). The applicability domain of the QSPR model was defined and an interpretation of selected model descriptors has been connected to previous experimental studies. A significant influence of the interpretable descriptors was put into experimental context and compared with previous studies and models. For example, the molar refractivity as a measure of size and polarizability of a molecule and the occurrence of important substructures such as a formamide group seem to decrease the removal rate constant. The contribution of lone electrons entering into resonance as well as the occurrence of fused rings were identified as influences for the increase of the degradability of micropollutants by ozonation.
Topics: Electrons; Environmental Pollutants; Ozone; Quantitative Structure-Activity Relationship; Water Purification
PubMed: 35872520
DOI: 10.1016/j.watres.2022.118866 -
Frontiers in Psychology 2019Two decades ago, the introduction of the Implicit Association Test (IAT) sparked enthusiastic reactions. With implicit measures like the IAT, researchers hoped to... (Review)
Review
Two decades ago, the introduction of the Implicit Association Test (IAT) sparked enthusiastic reactions. With implicit measures like the IAT, researchers hoped to finally be able to bridge the gap between self-reported attitudes on one hand and behavior on the other. Twenty years of research and several meta-analyses later, however, we have to conclude that neither the IAT nor its derivatives have fulfilled these expectations. Their predictive value for behavioral criteria is weak and their incremental validity over and above self-report measures is negligible. In our review, we present an overview of explanations for these unsatisfactory findings and delineate promising ways forward. Over the years, several reasons for the IAT's weak predictive validity have been proposed. They point to four potentially problematic features: First, the IAT is by no means a pure measure of individual differences in associations but suffers from extraneous influences like recoding. Hence, the predictive validity of IAT-scores should not be confused with the predictive validity of associations. Second, with the IAT, we usually aim to measure evaluation ("liking") instead of motivation ("wanting"). Yet, behavior might be determined much more often by the latter than the former. Third, the IAT focuses on measuring associations instead of propositional beliefs and thus taps into a construct that might be too unspecific to account for behavior. Finally, studies on predictive validity are often characterized by a mismatch between predictor and criterion (e.g., while behavior is highly context-specific, the IAT usually takes into account neither the situation nor the domain). Recent research, however, also revealed advances addressing each of these problems, namely (1) procedural and analytical advances to control for recoding in the IAT, (2) measurement procedures to assess implicit wanting, (3) measurement procedures to assess implicit beliefs, and (4) approaches to increase the fit between implicit measures and behavioral criteria (e.g., by incorporating contextual information). Implicit measures like the IAT hold an enormous potential. In order to allow them to fulfill this potential, however, we have to refine our understanding of these measures, and we should incorporate recent conceptual and methodological advancements. This review provides specific recommendations on how to do so.
PubMed: 31787912
DOI: 10.3389/fpsyg.2019.02483 -
Frontiers in Psychology 2022
PubMed: 35712131
DOI: 10.3389/fpsyg.2022.919658 -
Life Sciences Apr 2010Strategies for the design of bi- or multifunctional drugs are reviewed. A distinction is made between bifunctional drugs interacting in a monovalent fashion with two... (Review)
Review
Strategies for the design of bi- or multifunctional drugs are reviewed. A distinction is made between bifunctional drugs interacting in a monovalent fashion with two targets and ligands containing two distinct pharmacophores binding in a bivalent mode to the two binding sites in a receptor heterodimer. Arguments are presented to indicate that some of the so-called "bivalent" ligands reported in the literature are unlikely to simultaneously interact with two binding sites. Aspects related to the development of bi- or multifunctional drugs are illustrated with examples from the field of opioid analgesics. The drug-like properties of the tetrapeptide Dmt(1)[DALDA] with triple action as a micro opioid agonist, norepinephrine uptake inhibitor and releaser of endogenous opioid peptides to produce potent spinal analgesia are reviewed. Rationales for the development of opioid peptides with mixed agonist/antagonist profiles as analgesics with reduced side effects are presented. Progress in the development of mixed micro opioid agonist/delta opioid antagonists with low propensity to produce tolerance and physical dependence is reviewed. Efforts to develop bifunctional peptides containing a micro opioid agonist and a cholecystokinin antagonist or an NK1 receptor antagonist as analgesics expected to produce less tolerance and dependence are also reviewed. A strategy to improve the drug-like properties of bifunctional opioid peptide analgesics is presented.
Topics: Analgesics, Opioid; Animals; Binding Sites; Drug Design; Humans; Ligands; Narcotic Antagonists; Pain; Receptors, Opioid, delta; Receptors, Opioid, mu
PubMed: 19285088
DOI: 10.1016/j.lfs.2009.02.025 -
European Child & Adolescent Psychiatry May 2024Many transgender individuals face inequities, discrimination, and sometimes even a lack of transgender-specific knowledge in health care settings. Educational curricula... (Review)
Review
Many transgender individuals face inequities, discrimination, and sometimes even a lack of transgender-specific knowledge in health care settings. Educational curricula can address such disparities and help future health professionals to become more knowledgeable, confident, and well-prepared for addressing the needs of transgender individuals. This systematic review aims to summarize current training interventions about care of transgender individuals for health and allied health students, and to analyse the effects of the respective intervention. A total of six databases (Pubmed, MEDLINE, Scopus, Web of Science, Embase and SciSearch) were screened for original articles published between 2017 and June 2021. Search terms and eligibility criteria were pre-specified, and after a structured selection process 21 studies were included into further analysis. Extracted data contained information on general study properties, population, design, program format and outcomes of interest. A narrative synthesis was used to summarize detected results. Study quality was assessed for each individual study. A self-developed 18-item checklist combining criteria of two prior published tools was used to assess overall quality of quantitative studies. For qualitative studies a 10-item checklist by Kmet et al. [HTA Initiat, 2004] was applied. Eligible studies were designed for multiple health or allied health profession students, and varied widely regarding program format, duration, content, and assessed outcomes. Almost all (N = 19) interventions indicated improvements in knowledge, attitude, confidence and comfort levels or practical skills concerning care for transgender clients. Major limitations included the lack of long-term data, validated assessment tools, control groups and comparative studies. Training interventions contribute to prepare future health professionals to deliver competent and sensitive care and which may improve the prospective experienced health care reality of transgender individuals. However, currently there is no common consensus about best practice of education. Additionally, little is known about whether detected effects of training interventions translate into noticeable improvements for transgender clients. Further studies are warranted to assess the direct impact of specific interventions in the light of the respective target populations.
Topics: Humans; Allied Health Personnel; Clinical Competence; Curriculum; Health Knowledge, Attitudes, Practice; Health Personnel; Transgender Persons; Male; Female
PubMed: 37115277
DOI: 10.1007/s00787-023-02195-8 -
Colloids and Surfaces. B, Biointerfaces Jul 2022Previous studies implied that single crystalline rutile surfaces have the ability to guide the functionality of adsorbed blood plasma proteins. However, a clear relation...
Previous studies implied that single crystalline rutile surfaces have the ability to guide the functionality of adsorbed blood plasma proteins. However, a clear relation between the rutile crystallographic orientation and conformation of adsorbed proteins is still missing. Here, we examine the adsorption characteristics of human plasma fibrinogen (HPF) on atomically flat single rutile crystals with (110), (100), (101) and (001) facets. By direct visualization of individual protein molecules through atomic force microscopy (AFM) imaging, the distinct conformations of HPF were determined depending on rutile surface crystallographic orientation. In particular, dominant trinodular and globular conformation was found on (110) and (001) facets, respectively. The observed variations of HPF conformation were reasoned from the surface water contact angle and surface energy point of view. By analyzing AFM-based force measurements, statistically significant changes in surface energies of rutile surfaces covered with HPF were determined and linked to HPF conformation. Furthermore, the facet-dependent structural rearrangement of HPF was indirectly confirmed through deconvolution of high-resolution X-ray photoelectron spectroscopy (XPS) carbon and nitrogen spectra. The globular, and thus native-like HPF conformation observed on (001) facet, was reflected in the lowest level of amino group formation. We propose that the mechanism behind the crystallographic orientation-induced HPF conformation is driven by the facet-specific surface hydrophilicity and energy. From the biomedical material perspective, our results demonstrate that the conformation of HPF can be guided by controlling the crystallographic orientation of the underlying material surface. This might be beneficial to the field of titanium-based biomaterials design and development.
Topics: Adsorption; Biocompatible Materials; Fibrinogen; Hemostatics; Humans; Microscopy, Atomic Force; Surface Properties; Titanium
PubMed: 35487071
DOI: 10.1016/j.colsurfb.2022.112506 -
Scientific Reports Dec 2022The generation of tailored light fields with spatially controlled intensity and phase distribution is essential in many areas of science and application, while creating...
The generation of tailored light fields with spatially controlled intensity and phase distribution is essential in many areas of science and application, while creating such patterns remotely has recently defined a key challenge. Here, we present a fiber-compatible concept for the remote generation of complex multi-foci three-dimensional intensity patterns with adjusted relative phases between individual foci. By extending the well-known Huygens principle, we demonstrate, in simulations and experiments, that our interference-based approach enables controlling of both intensity and phase of individual focal points in an array of spots distributed in all three spatial directions. Holograms were implemented using 3D nano-printing on planar substrates and optical fibers, showing excellent agreement between design and implemented structures. In addition to planar substrates, holograms were also generated on modified single-mode fibers, creating intensity distributions consisting of about 200 individual foci distributed over multiple image planes. The presented scheme yields an innovative pathway for phase-controlled 3D digital holography over remote distances, yielding an enormous potential application in fields such as quantum technology, life sciences, bioanalytics and telecommunications. Overall, all fields requiring precise excitation of higher-order optical resonances, including nanophotonics, fiber optics and waveguide technology, will benefit from the concept.
PubMed: 36463325
DOI: 10.1038/s41598-022-25380-2