ABSTRACT
Nicotine is known to affect cell proliferation and differentiation, two processes vital to proper development of the mandible. The mandible, the lower jaw in mammals and fish, plays a crucial role in craniofacial development. Malformation of the jaw can precipitate a plethora of complications including disrupting development of the upper jaw, the palate, and or impeding airway function. The purpose of this study was to test the hypothesis that in utero nicotine exposure alters the development of the murine mandible in a dose dependent manner. To test this hypothesis, wild type C57BL6 mice were used to produce in utero nicotine exposed litters by adding nicotine to the drinking water of pregnant dams at concentrations of 0 µg/ml (control), 50 µg/ml (low), 100 µg/ml (medium), 200 µg/ml (high) throughout pregnancy to birth of litters mimicking clinically relevant nicotine exposures. Resultant pups revealed no significant differences in body weight however, cephalometric investigation revealed several dimensions affected by nicotine exposure including mandibular ramus height, mandibular body height, and molar length. Histological investigation of molars revealed an increase in proliferation and a decrease in apoptosis with nicotine exposure. These results demonstrate the direct effects of nicotine on the developing mandible outside the context of tobacco use, indicating that nicotine use including tobacco alternatives, cessation methods, and electronic nicotine delivering products may disrupt normal growth and development of the craniofacial complex.
Subject(s)
Mandible/embryology , Nicotine/adverse effects , Organogenesis/drug effects , Animals , Biomarkers , Cell Proliferation , Female , Immunohistochemistry , Male , Mandible/anatomy & histology , Mandible/cytology , Maternal Exposure , Mice , Molar/metabolism , Pregnancy , Prenatal Exposure Delayed EffectsABSTRACT
Optical imaging techniques for biofilm observation, like laser scanning microscopy, are not applicable when investigating biofilm formation in opaque porous media. X-ray micro-tomography (X-ray CMT) might be an alternative but it finds limitations in similarity of X-ray absorption coefficients for the biofilm and aqueous phases. To overcome this difficulty, barium sulphate was used in Davit et al. (2011) to enable high-resolution 3D imaging of biofilm via X-ray CMT. However, this approach lacks comparison with well-established imaging methods, which are known to capture the fine structures of biofilms, as well as uncertainty quantification. Here, we compare two-photon laser scanning microscopy (TPLSM) images of Pseudomonas Aeruginosa biofilm grown in glass capillaries against X-ray CMT using an improved protocol where barium sulphate is combined with low-gelling temperature agarose to avoid sedimentation. Calibrated phantoms consisting of mono-dispersed fluorescent and X-ray absorbent beads were used to evaluate the uncertainty associated with our protocol along with three different segmentation techniques, namely hysteresis, watershed and region growing, to determine the bias relative to image binarization. Metrics such as volume, 3D surface area and thickness were measured and comparison of both imaging modalities shows that X-ray CMT of biofilm using our protocol yields an accuracy that is comparable and even better in certain respects than TPLSM, even in a nonporous system that is largely favourable to TPLSM.
Subject(s)
Biofilms , Imaging, Three-Dimensional/methods , Microscopy, Confocal/methods , X-Ray Microtomography/methods , Contrast Media , Porosity , Pseudomonas aeruginosa/physiologyABSTRACT
Adipocytes, apart from their critical role as the energy storage depots, contribute to the composition of the tumor microenvironment. Our previous studies based on a single hematopoietic stem cell (HSC) transplantation model, have revealed a novel source of adipocytes from HSCs via monocyte/macrophage progenitors. Herein, we extend these studies to examine the role of HSC-derived adipocytes (HSC-Ad) in tumor progression. When cultured under adipogenic conditions, bone marrow-derived monocytic progenitors differentiated into adipocytes that accumulated oil droplets containing triglyceride. The adipokine array and ELISAs confirmed secretion of multiple adipokines by HSC-Ad. These adipocytes underwent further development in vivo when injected subcutaneously into C57Bl/6 mice. When co-injected with melanoma B16F1 cells or breast cancer E0771 cells into syngeneic C57Bl/6 mice, HSC-Ad not only accelerated both melanoma and breast tumor growth, but also enhanced vascularization in both tumors. Conditioned media from HSC-Ad supported B16F1 and E0771 cell proliferation and enhanced cell migration in vitro. Among the HSC-Ad secreted adipokines, insulin-like growth factor 1 (IGF-1) played an important role in E0771 cell proliferation. Hepatocyte growth factor (HGF) was indispensable for B16F1 cell migration, whereas HGF and platelet-derived growth factor BB (PDGF-BB) collectively contributed to E0771 cell migration. Expression levels of receptors for IGF-1, HGF, and PDGF-BB correlated with their differential roles in B16F1 and E0771 cell proliferation and migration. Our data suggest that HSC-Ad differentially regulate tumor behavior through distinct mechanisms.
ABSTRACT
Breast cancer is a worldwide health issue as it represents the leading cause of cancer in women and the second-leading cause of cancer-related mortality in women, with an increasing incidence. Nothing speaks more clearly to the shocking breast cancer health disparities than the fact that African American (AA) women are as likely to get breast cancer as Caucasian American (CA) women, yet have a higher breast cancer death rate. It is becoming increasingly apparent that racial disparity in cancer exists due to molecular differences in tumor biology as well as, or in addition to, socioeconomic and standard of care issues (Albain, Unger, Crowley, Coltman, & Hershman, 2009). A greater understanding of the risk factors and biological links associated with breast cancer, will significantly impact AA communities due to the higher deaths associated with this disease in this population. microRNAs are small noncoding RNA molecules that were recently discovered as major players in the regulation of many diseases including cancer. Although, there are many studies that have investigated the role of miRNAs in breast cancer, few have investigated their role if any in breast cancer disparities. This review serves to summarize the current published literature that is involved in the study of microRNAs and their impact on breast cancer disparities.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Ethnicity/statistics & numerical data , Health Status Disparities , MicroRNAs/genetics , Tumor Microenvironment , Female , Humans , Risk FactorsABSTRACT
INTRODUCTION: Today the concept of apathy is subject to many questions. This psychological state is present and predominant in different disorders such as neurodegenerative and psychiatric diseases or neurological acquired disorders. Apathy is a part of the clinical vocabulary, however, we can note that in the literature there remains confusion in its definition, and we can find an amalgam with other clinical symptoms. OBJECTIVES: The aim of this review is to provide a clarification of the concept of apathy in clinical practice in schizophrenia as well as to highlight the gaps that exist. LITERATURE FINDINGS: Apathy belongs to the negative symptoms of schizophrenia. For its understanding, it is necessary to define apathy as a multidimensional syndrome (cognitive, emotional, and behavioral) manifesting as a quantitative reduction of voluntary behaviors directed toward one or several goals. However, at present, we are witnessing a reductionist and simplistic conception of the syndrome of apathy and this especially in the Anglo-Saxon literature. Several authors reduce apathy to its behavioral component, so in other words, to avolition/amotivation. Avolition refers to a loss of self-initiated and spontaneous behaviors. In this definition only observable behavior is taken into account and not the underlying mechanisms (cognitive and emotional). In order to understand the syndrome of apathy, it is necessary to have a holistic and multidimensional outlook. Some authors have proposed diagnostic criteria for apathy by taking into account the different dimensions of apathy. Moreover not only is apathy confused with avolition, but it is also still difficult to distinguish it from depression. Apathy and depression share common clinical signs (i.e. loss of interest), but they also have distinct clinical signs (lack of motivation for apathy, and suicidal ideation for depression). Authors have shown that the presence of one symptom (apathy or depression) does not predict the presence of the other. An apathetic patient does not have to be necessarily in a depressive state and vice versa. However, to our knowledge, there is no data capable of distinguishing depression from apathy in schizophrenia, and knowing what is the part of one and the other when the patient has both symptoms. In addition, we can see that the confusion that persists between those two symptoms also stems from assessment tools. Indeed, some assessment tools such as the Montgomery and Asberg Depression Rating Scale (MARDS) have an apathy subscale. Therefore, this scale does not only evaluate depression. Regarding the assessment of apathy in schizophrenia, there are specific and nonspecific tools. Nonspecific tools define apathy differently. For this reason, authors have proposed to measure apathy by using analytic factors of negative symptoms. In this case, apathy is going to be assessed by the factor "motivation/pleasure" including anhedonia, asociality and avolition. This factor will provide the possibility of a better assessment of apathy. Concerning specific scales (like AES), there are gaps such as a lack of standardization in the execution and the quotation. Furthermore, no scale takes into account the factors causing apathy. CONCLUSION: Knowing the reasons for apathy is necessary because this syndrome is frequent in schizophrenia, and it is found in the different phases of this disease (prodromal, first episode psychosis, and chronic). In addition, apathy has significant functional consequences on the patient's quality of life, as well as on his or her global functioning. Indeed, apathy impacts on his or her social and professional life. Patients with schizophrenia have a loss of autonomy, less employment and social withdrawal. Consequently, interest in its drug or treatment it is obvious. However, drug and non-drug treatments are not specific to apathy and therefore little effective on this syndrome. Implications to stimulate future research are presented.
Subject(s)
Apathy , Schizophrenia/diagnosis , Schizophrenic Psychology , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Humans , Psychiatric Status Rating Scales/statistics & numerical data , PsychometricsABSTRACT
This article addresses the issue of representing electroencephalographic (EEG) signals in an efficient way. While classical approaches use a fixed Gabor dictionary to analyze EEG signals, this article proposes a data-driven method to obtain an adapted dictionary. To reach an efficient dictionary learning, appropriate spatial and temporal modeling is required. Inter-channels links are taken into account in the spatial multivariate model, and shift-invariance is used for the temporal model. Multivariate learned kernels are informative (a few atoms code plentiful energy) and interpretable (the atoms can have a physiological meaning). Using real EEG data, the proposed method is shown to outperform the classical multichannel matching pursuit used with a Gabor dictionary, as measured by the representative power of the learned dictionary and its spatial flexibility. Moreover, dictionary learning can capture interpretable patterns: this ability is illustrated on real data, learning a P300 evoked potential.
Subject(s)
Electroencephalography/methods , Learning/physiology , Algorithms , Brain-Computer Interfaces , Electrodes , Electroencephalography/statistics & numerical data , Electroencephalography Phase Synchronization , Event-Related Potentials, P300 , Humans , Models, Neurological , Multivariate Analysis , Reproducibility of Results , Signal Processing, Computer-Assisted , SoftwareABSTRACT
INTRODUCTION: New challenges arise in medicine, particularly in psychiatry. In the near future, psychiatrists' role may evolve into management of mental health care teams (GPs, nurses, psychologists ) thus creating the need for charisma and leadership. Charisma is defined as « a quality that allows it's possessor to exercise influence, authority over a group ¼; leadership as « the function, the position of chief, and by extension, a dominant position ¼. AIM OF THE STUDY: To offer some reflections on charisma and leadership and the ways to develop them in three situations common in clinical practice: dual communication (between caregivers or with patients), oral communication (e.g., during a symposium) and managing a mental health care team. METHOD: Medline (1966-hits) and Web of Science (1975-hits) were explored according to the PRISMA criteria. The research paradigm was [(psychiatrist OR physician) AND mental health AND (leadership OR charisma)]. RESULTS: Two hundred and eighty articles were found, but only 34 corresponded to our subject and were included in the qualitative analysis. The leader must first ask himself/herself about his/her vision of the future, so as to share it with passion with his/her mental health team. Charisma and leadership are based on several values, among which we can mention: providing understandable, personalized care for the patient, in continuity and confidentiality; adapting care to the general population's request, maintaining one's own physical and mental health, submitting one's daily practice to peer review, engaging in continuous improvement of one's practices in response to new requirements, and recognizing that research and instruction are part of an M.D's professional obligations. The clinician will work on ways to develop his/her own charisma, through interactions with peers and team members, the care of his/her appearance (especially for first meetings) and workplace, and through positive reinforcement (some cognitive-behavioral techniques like assertiveness have been proposed to enhance the charisma, e.g., visualization and affirmation). Leadership does not depend on hierarchical position and administrative responsibilities: leaders should learn to manage and harmonize the different types of personalities within his/her team, paying special attention to passive-aggressive attitudes. We recall here some techniques to improve charisma during oral communication, such as making relationships with people by calling them by their names, making reference to things and people that the audience can identify with (like sport or cooking), using one's own style without trying to imitate someone else, focusing on one major idea, being brief and using anecdotes, using silences effectively and finally having good non-verbal communication. The conclusion should never be neglected, as an audience especially remembers the beginning and the end of a presentation. Although some features are common to all charismatic leaders (dominance, self-confidence, high energy level), a recent theory of leadership (called contingency theory) seeks to examine how different leadership styles can adapt to circumstances. This theory focuses more on the vision, passion, determination and courage of the leader and depends not only on their intrinsic qualities. No research has indeed shown individual characteristics that differentiate leaders from followers. However, doctors have not been prepared in their training to acquire leadership skills that they can use to adapt to the circumstances of their clinical practice. The most important qualities expected of a leader according to the current leadership theorists are: listening, communication, stress management, development of other's capacities, feedback, introspection and risk taking. Moreover, leadership involves positive reinforcement of the team while maintaining the feeling of individual autonomy, and being able to take an innovative decision alone with shared optimism. There is no need to have great management responsibilities in order to succeed in leadership. We reiterate the importance for a charismatic leader to smile, to be able to mock oneself and to regulate one's emotions. CONCLUSION: Charisma seems to be an essential dimension for effective leadership and team management. Beyond psychiatry, we believe these reflections to be useful for all branches of medicine.
Subject(s)
Character , Leadership , Patient Care Team/trends , Physician Executives/trends , Psychiatry/trends , Caregivers/psychology , Cooperative Behavior , Emotional Intelligence , Forecasting , France , Humans , Interdisciplinary Communication , Personnel Management/trends , Physician Executives/psychology , Physician's Role/psychology , Physician-Patient Relations , Professional-Family RelationsABSTRACT
INTRODUCTION: Seventy-five percent of patients with blood-injection-injury phobia (BII-phobia) report a history of fainting in response to phobic stimuli. This specificity may lead to medical conditions remaining undiagnosed and untreated, incurring considerable cost for the individual and society. The psychophysiology of BII-phobia remains poorly understood and the literature on effective treatments has been fairly sparse. Aims of the systematic review: to synthesize the psychophysiology of BII-phobia and to propose a systematic review of the literature on effectiveness of different treatments evaluated in this indication. RESULTS: Firstly, the most distinct feature of the psychophysiology of BII-phobia is its culmination in a vasovagal syncope, which has been described as biphasic. The initial phase involves a sympathetic activation as is typically expected from fear responses of the fight-flight type. The second phase is characterized by a parasympathetic activation leading to fainting, which is associated with disgust. Subjects with syncope related to BII-phobia have an underlying autonomic dysregulation predisposing them to neurally mediated syncope, even in the absence of any blood or injury stimulus. Many studies report that BII-phobic individuals have a higher level of disgust sensitivity than individuals without any phobia. Secondly, behavioral psychotherapy techniques such as exposure only, applied relaxation, applied tension, and tension only, have demonstrated efficacy with no significant difference between all these techniques. The disgust induction has not improved effectiveness of exposure. CONCLUSION: We have explained the psychophysiology of BII-phobia, the understanding of which is required to study and validate specific techniques, in order to improve the prognosis of this disorder, which is a public health issue.
Subject(s)
Accidents/psychology , Blood , Injections/psychology , Phobic Disorders/physiopathology , Phobic Disorders/therapy , Syncope, Vasovagal/physiopathology , Wounds and Injuries/psychology , Arousal/physiology , Clinical Trials as Topic , Cognitive Behavioral Therapy , Diagnosis, Differential , Fear/physiology , Humans , Phobic Disorders/psychology , Prognosis , Psychophysiology , Relaxation Therapy , Syncope, Vasovagal/psychology , Syncope, Vasovagal/therapyABSTRACT
INTRODUCTION: Toxoplasma gondii is the most common protozoan parasite in developed nations. Up to 43% of the French population may be infected, depending on eating habits and exposure to cats, and almost one third of the world human's population may be infected. Two types of infection have been described: a congenital form and an acquired form. Although the medical profession treats these latent cases as asymptomatic and clinically unimportant, results of animal studies and recent studies of personality profiles, behavior, and psychomotor performance have led to reconsider this assumption. PRECLINICAL DATA: Among rats: parasite cysts are more abundant in amygdalar structures than those found in other regions of the brain. Infection does not influence locomotion, anxiety, hippocampal-dependent learning, fear conditioning (or its extinction) and neophobia in rats. Rats' natural predator is the cat, which is also T. gondii's reservoir. Naturally, rats have an aversion to cat urine, but the parasite suppresses this aversion in rats, thus influencing the infection cycle. Tachyzoites may invade different types of nervous cells, such as neurons, astrocytes and microglial cells in the brain, and Purkinje cells in cerebellum. Intracellular tachyzoites manipulate several signs for transduction mechanisms involved in apoptosis, antimicrobial effectors functions, and immune cell maturation. Dopamine levels are 14% higher in mice with chronic infections. These neurochemical changes may be factors contributing to mental and motor abnormalities that accompany or follow toxoplasmosis in rodents and possibly in humans. Moreover, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro with synergistic activity. CLINICAL DATA: The effects of the parasite are not due to the manipulation in an evolutionary sense but merely due to neuropathological or neuroimmunological effects of the parasite's presence. Toxoplasmosis and schizophrenia: epidemiological studies point to a role for toxoplasmosis in schizophrenia's etiology, probably during pregnancy and early life, this association being congruent with studies in animal models indicating that animal exposures of the developing brain to infectious agents or immune modulating agents can be associated with behavioral changes that do not appear until the animal reaches full maturity. Psychiatric patients have increased rates of toxoplasmic antibodies, the differences between cases and controls being greatest in individuals who are assayed near the time of the onset of their symptoms. The increase of dopamine in the brain of infected subjects can represent the missing link between toxoplasmosis and schizophrenia. Toxoplasmosis and Obsessive Compulsive Disorder (OCD): the seropositivity rate for anti-T. gondii IgG antibodies among OCD patients is found to be significantly higher than the rate in healthy volunteers. Infection of basal ganglia may be implicated in the pathogenesis of OCD among Toxoplasma seropositive subjects. Toxoplasmosis and personality: infected men appear to be more dogmatic, less confident, more jealous, more cautious, less impulsive and more orderly than others. Conversely, infected women seem warmest, more conscientious, more insecure, more sanctimonious and more persistent than others. It is possible that differences in the level of testosterone may be responsible for the observed behavioral differences between Toxoplasma-infected and Toxoplasma-free subjects. CONCLUSION: In the future two major avenues for research seem essential. On one hand, prospective studies and research efforts must still be carried out to understand the mechanisms by which the parasite induces these psychiatric disorders. On the other hand, it has not yet been demonstrated that patients with positive toxoplasmic serology may better respond to haloperidol's or valproic acid's antiparasitic activity. These results may appear as a major issue in the drug's prescribing choices and explain variability in response to the treatment of patients with schizophrenia that is not explained by the genetic polymorphism.
Subject(s)
Mental Disorders/diagnosis , Mental Disorders/parasitology , Toxoplasma/pathogenicity , Toxoplasmosis/complications , Toxoplasmosis/diagnosis , Adult , Animals , Brain/parasitology , Cats , Disease Models, Animal , Dopamine/metabolism , Female , Humans , Infant , Infant, Newborn , Male , Mental Disorders/psychology , Mice , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/parasitology , Obsessive-Compulsive Disorder/psychology , Personality Disorders/diagnosis , Personality Disorders/parasitology , Personality Disorders/psychology , Pregnancy , Schizophrenia/diagnosis , Schizophrenia/parasitology , Schizophrenic Psychology , Toxoplasmosis/psychology , Toxoplasmosis/transmission , Toxoplasmosis, Congenital/diagnosis , Toxoplasmosis, Congenital/parasitology , Toxoplasmosis, Congenital/transmissionABSTRACT
INTRODUCTION: Important data was recently published on the potential genotoxic or carcinogenic effects of antipsychotics, as well as on their cytotoxic properties on cancer cells, that must be considered by psychiatrists in the benefit/risk ratio of their prescriptions. AIM OF THE STUDY: To answer whether or not antipsychotics, as a class or only some specific molecules, may influence cancer risk among treated patients. METHODS ELIGIBILITY CRITERIA: All studies (in vitro, animal studies and human studies) concerning effects of antipsychotic drugs on cancer development were included. The search paradigm [neoplasms AND (antipsychotic agents OR neuroleptic OR phenothiazine)] was applied to Medline (1966-present) and Web of Science (1975-present). RESULTS: Ninety-three studies were included in the qualitative synthesis. Results can be summarized as follows: (1) patients with schizophrenia may be less likely to develop cancer than the general population, (2) antipsychotics as a class cannot be considered at the moment as at risk for cancer, even if some antipsychotics have shown carcinogenic properties among rodents, (3) phenothiazines seem to have antiproliferative properties that may be useful in multidrug augmentation strategies in various cancer treatments, but their bad tolerance may decrease usage amongst non-psychotic patients, and (4) clozapine appears to have a separate status given that this molecule shows antiproliferative effects implied in agranulocytosis as well as a potential increased risk for leukemia. CONCLUSION: Benefit/risk ratio regarding cancer risk is in favor of treating patients with schizophrenia with antipsychotic drugs. The practicing clinician should be reassuring on the subject of cancer risk due to antipsychotic drugs.
Subject(s)
Antipsychotic Agents/adverse effects , Neoplasms/chemically induced , Animals , Female , Humans , Male , Mice , Risk FactorsABSTRACT
OBJECTIVE: To evaluate the longitudinal influence of family history (FH) of Alzheimer disease (AD) and apolipoprotein E ε4 allele (APOE4) on brain atrophy and cognitive decline over 4 years among asymptomatic middle-aged individuals. METHODS: Participants were cognitively healthy adults with (FH+) (n = 60) and without (FH-) (n = 48) a FH of AD (mean age at baseline 54 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention. They underwent APOE genotyping, cognitive testing, and an MRI scan at baseline and 4 years later. A covariate-adjusted voxel-based analysis interrogated gray matter (GM) modulated probability maps at the 4-year follow-up visit as a function of FH and APOE4. We also examined the influence of parent of origin on GM atrophy. Parallel analyses investigated the effects of FH and APOE4 on cognitive decline. RESULTS: Neither FH nor APOE4 had an effect on regional GM or cognition at baseline. Longitudinally, a FH × APOE4 interaction was found in the right posterior hippocampus, which was driven by a significant difference between the FH+ and FH- subjects who were APOE4-. In addition, a significant FH main effect was observed in the left posterior hippocampus. No significant APOE4 main effects were detected. Persons with a maternal history of AD were just as likely as those with a paternal history of AD to experience posterior hippocampal atrophy. There was no longitudinal decline in cognition within the cohort. CONCLUSION: Over a 4-year interval, asymptomatic middle-aged adults with FH of AD exhibit significant atrophy in the posterior hippocampi in the absence of measurable cognitive changes. This result provides further evidence that detectable disease-related neuroanatomic changes do occur early in the AD pathologic cascade.
Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/pathology , Apolipoprotein E4/genetics , Hippocampus/pathology , Alzheimer Disease/prevention & control , Analysis of Variance , Atrophy/diagnosis , Cognition , Cohort Studies , Fathers , Female , Genotype , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Medical History Taking , Middle Aged , Mothers , Neuropsychological Tests , Predictive Value of TestsABSTRACT
One function of bone marrow megakaryocytes (MKs) is the controlled release of platelets into the circulation. Over the past few years, molecular mechanisms that contribute to MK development and differentiation have begun to be elucidated. This review provides a brief overview of megakaryopoiesis and platelet function, and the importance of selected hematopoietic transcription factors (including GATA-1, FOG, Fli-1, AML1, and NF-E2) and target genes in this biological process. In addition, a discussion of human diseases affecting megakaryopoiesis and mouse models of thrombocytopenia are presented with emphasis on how these systems have and will continue to provide further insights into mechanisms that control the biological functions of the megakaryocytic cell lineage. Ultimately, such knowledge may provide the basis for novel therapeutic approaches for modulation of platelet number and function.
Subject(s)
Thrombopoiesis/genetics , Animals , Gene Expression Regulation , Humans , Models, Molecular , Signal Transduction , Transcription Factors/metabolism , Transcription, GeneticABSTRACT
OBJECTIVE: To determine whether elderly individuals with type 2 diabetes or impaired glucose tolerance are at increased risk for cognitive impairment compared with individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS: Elderly Hispanic individuals (n = 414) and non-Hispanic white individuals (n = 469) aged > or =65 years, randomly selected from the Medicare rolls of Bernalillo County (Albuquerque), NM, were recruited for an interview/examination that included an evaluation of glucose tolerance. Information on nine tests of cognitive function and two measures of depression allowed comparisons between diabetic status and these functions. Comparisons also were made between glycosolated hemoglobin concentrations and these cognitive tests in the 188 participants with diabetes. RESULTS: None of the mean scores on the tests of cognitive function was significantly lower in the participants with diabetes compared with those participants with normal glucose tolerance after adjustments for ethnicity, sex, age, level of education, and presence of depression, with or without elimination of those with dementia (Mini-Mental State Exam <18). Interestingly, participants with impaired glucose tolerance tended to score higher than those with normal glucose tolerance. No significant associations were found between glycosolated hemoglobin concentrations and cognitive test scores in participants with diabetes. CONCLUSIONS: We could not show any increased risk for cognitive impairment in participants with diabetes compared with those with normal glucose tolerance after adjustments for ethnicity, sex, age, education, and presence of depression, before or after elimination of dementia in this random sample from a biethnic population of predominantly community-dwelling elders.
Subject(s)
Cognition , Diabetes Mellitus, Type 2/psychology , Ethnicity , Glucose Intolerance/psychology , Aged , Attention , Blood Glucose/metabolism , Centers for Medicare and Medicaid Services, U.S. , Diabetes Mellitus, Type 2/blood , Educational Status , Glucose Intolerance/blood , Glycated Hemoglobin/analysis , Health Surveys , Hispanic or Latino , Humans , Intelligence , Learning , Medicare , Memory , Mental Status Schedule , Neuropsychological Tests , New Mexico , Reference Values , United States , Wechsler Scales , White PeopleABSTRACT
Prominent among molecules that control neovascular processes is vascular endothelial growth factor (VEGF). The VEGF ligands comprise a family of well-studied mitogens/permeability factors that bind cell surface receptor tyrosine kinases. Targets include VEGF receptor-1/Flt1 and VEGF receptor-2/Flk1. Mice lacking genes for VEGF ligand or VEGF receptor-2 die early in gestation, making it difficult to determine the precise nature of underlying endothelial cellular behavior(s). To examine the effect(s) of VEGF signaling on cell behavior in detail, we conducted loss-of-function studies using avian embryos. Injection of soluble VEGFR-1 results in malformed vascular networks and the absence of large vessels. In the most severe cases embryos exhibited vascular atresia. Closely associated with the altered phenotype was a clear endothelial cell response-a marked decrease in cell protrusive activity. Further, we demonstrate that VEGF gain of function strikingly increased cell protrusive activity. Together, our data show that VEGF/VEGF receptor signaling regulates endothelial cell protrusive activity, a key determinant of blood vessel morphogenesis. We propose that VEGF functions as an instructive molecule during de novo blood vessel morphogenesis.
Subject(s)
Endothelial Growth Factors/physiology , Endothelium, Vascular/embryology , Lymphokines/physiology , Animals , Endothelial Growth Factors/metabolism , Lymphokines/metabolism , Mice , Proto-Oncogene Proteins/metabolism , Quail/embryology , Receptor Protein-Tyrosine Kinases/metabolism , Signal Transduction , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-1 , Vascular Endothelial Growth FactorsABSTRACT
OBJECTIVES: 1) To compare serum vitamin B12, C and folate concentrations in a randomly selected sample of elderly (age 65 years or older) male and female Hispanics and nonHispanic whites (NHW) and 2) to examine associations between serum B12, C and folate concentrations compared to measures of cognitive and affective (depression) functions. METHODS: Equal numbers of male and female Hispanics and NHW were randomly sampled from the Health Care Financing Administration (Medicare) registrant list for Bernalillo County, New Mexico, and asked to volunteer for a paid home interview followed by a paid comprehensive interview/examination covering health and health-related issues. In addition to serum determinations of B12, C and folate, associations were examined between these vitamins and measures of cognitive and affective functions. RESULTS: Males and Hispanics had lower serum vitamin B12, C and folate concentrations than females and NHW respectively. Participants taking a multivitamin supplement (MVI) had higher serum vitamin concentrations than those not taking MVI. There were significant associations between serum folate concentrations and measures of cognitive function, not seen with B12 or C, nor between any of the vitamins and affective function. CONCLUSIONS: Hispanics, even after adjustments for gender, age, vitamin supplementation, vitamin content of dietary foods, education and household income, had lower serum concentrations of B12, C and folate than NHW. The most significant associations observed were those between serum folate and various measures of cognitive function, even after adjusting for presence of depression.
Subject(s)
Affect , Aging , Ascorbic Acid/blood , Cognition , Folic Acid/blood , Vitamin B 12/blood , Aged , Female , Hispanic or Latino , Humans , Male , New Mexico , Vitamins/administration & dosageABSTRACT
OBJECTIVES: To evaluate the association between hypothyroidism, and the health status of older Hispanic and non-Hispanic white (NHW) men and women. To accomplish this, we determined the prevalences of the treated and untreated conditions and examined the associations between an elevated serum thyroid stimulating hormone (TSH) and cognitive and affective (mood) functions and the prevalences of symptoms and comorbidity, specifically coronary heart disease (CHD), diabetes, hypertension, and hyperlipidemia. DESIGN AND SETTING: A cross-sectional study of equal numbers of Hispanic and NHW men and women selected randomly from the Health Care Financing Administration (Medicare) rolls and recruited for a home interview followed by a 4-hour interview/examination in a senior health clinic. PARTICIPANTS: 883 volunteers, mean age 74.1 years, participated in interviews/examinations MEASUREMENTS: Serum TSH was determined in 825 participants responding to questions about thyroid replacement therapy. Serum free thyroxine (free T4) concentrations were determined in 139 participants with elevated TSH concentrations (>4.6 microU/mL). Symptoms, cognitive tests, a screen for depression, comorbidities (e.g., CHD), and risk factors (e.g., lipid abnormalities, diabetes, and hypertension) were compared in participants with high versus normal TSH values. RESULTS: Subclinical hypothyroidism is more common in women than in men and in non-Hispanic white women compared with Hispanic women. No differences were observed between participants with TSH elevations from 4.7 to 10 microU/mL and those with normal TSH concentrations, and only a few differences were observed in those with TSH concentrations above 10. CONCLUSIONS: Subclinical hypothyroidism is a common condition in community-living older people, especially women. However, it appeared to have no effect on any of the measures of health status utilized until serum TSH concentrations exceeded 10 microU/mL, and even then the effects were rarely significant.
Subject(s)
Hispanic or Latino , Hypothyroidism/ethnology , Urban Population , White People , Age Distribution , Aged , Chronic Disease , Cross-Sectional Studies , Female , Hispanic or Latino/psychology , Hispanic or Latino/statistics & numerical data , Humans , Hypothyroidism/diagnosis , Hypothyroidism/psychology , Linear Models , Male , Neuropsychological Tests , New Mexico/epidemiology , Prevalence , Prospective Studies , Risk Factors , Sex Distribution , Urban Population/statistics & numerical data , White People/psychology , White People/statistics & numerical dataABSTRACT
OBJECTIVE: To determine the extent to which individual changes in systolic blood pressure (SBP) over a 30-year interval are associated with differential neuropsychological outcomes in old age. METHODS: Seven hundred seventeen survivors from the Western Collaborative Group Study, a longitudinal study of cardiovascular risk factors now in its 38th year of follow-up, with blood pressures measured in middle age (mean=45 years) and in old age (mean=75 years) and neuropsychological tests administered at follow-up were included in this analysis. Participants were grouped according to 30-year change in SBP (increased, decreased, or "normal"). Analyses focused on comparisons of neuropsychological performance of "high SBP trackers" (ie, those with persistent SBP>/=140 mm Hg throughout adult life) and of SBP "decreasers" with the performance of those whose SBP was either stable or changed in an expected way over time. RESULTS: Only 7.5% of participants had elevated SBP in middle age, but 43.8% of participants had elevated SBP in old age. After adjustment for age, education, depression, clinically defined stroke, and use of antihypertensive medications and after exclusion of individuals with impaired cognitive performance at follow-up, high SBP trackers, 5.0% (n=36), performed consistently less well than the "normal" SBP subgroups on a composite measure of verbal learning and memory (P=0.04). When compared with the "normal" SBP subgroup, the SBP decreasers, 5.3% (n=38), performed less well on speeded performance (P=0.03). CONCLUSIONS: There is a relatively small group of people who maintain elevated SBP throughout their adult lives. These persons are at increased risk for reduced verbal learning and memory function. There is also a group of individuals who experience a decrease in SBP and who are at risk for decreased psychomotor speed. Delineation of these 2 SBP subgroups may lead to further clarification of the effects of SBP on neurobehavioral function in older adults.
Subject(s)
Aging/physiology , Blood Pressure/physiology , Cognition/physiology , Neuropsychological Tests/statistics & numerical data , Adult , Aged , Aged, 80 and over , Humans , Hypertension/epidemiology , Hypertension/physiopathology , Longitudinal Studies , Male , Middle Aged , Neuropsychology , Risk Factors , SystoleABSTRACT
The purpose of this paper is to report on the outcome of recruitment and participation rate in the New Mexico Elder Health Survey. This survey is the first community based epidemiological survey to examine health and health related issues of elderly (65 years or older) Hispanics and non-Hispanic whites in Bernalillo County (Albuquerque), New Mexico. This survey was conducted from May 1993 to September 1995. Subjects (N=2200) were randomly selected from the list of 50,700 Medicare recipients residing in Bernalillo County and stratified by ethnicity and gender. Hispanics were identified using a computer program that selects Hispanic surname patterns and ethnicity was verified by self report. Subjects participated in a home interview, followed by an interview and examination in a senior health clinic. Use of the Medicare list resulted in 75.7% (N=1666) of subjects being contacted. Of the 1666 subjects available, 1130 (67.8%) completed a home interview and 883 (54%) completed the full examination. There were no significant differences in participation by ethnicity, but there were significant differences by gender, with women less likely to participate. The mean age of participants was 74 years, age range 65 to 100. Hispanic elderly demonstrated greater economic poverty and lower levels of formal education. Our survey results show that the elderly and Hispanic elderly can be successfully recruited to participate in a research study. This paper is the first to summarize the details of the survey design, present the results of recruitment and participation, and describe the survey participants.
Subject(s)
Aged , Health Surveys , Age Factors , Aged, 80 and over , Data Interpretation, Statistical , Education , Female , Hispanic or Latino , Humans , Income , Interviews as Topic , Male , New Mexico , Research Design , Sampling Studies , Sex Factors , Socioeconomic Factors , White PeopleABSTRACT
The authors compared the Mini-Mental State Examination (MMSE) and the Fuld Object-Memory Exam (FULD) in a Hispanic non-immigrant population in New Mexico. Results demonstrated that performance on the MMSE was affected by lower education and income levels. Performance on the FULD was not affected by these variables. Among persons with limited education and lower income, the FULD may provide a better means of screening for cognitive deficit than measures such as the MMSE.
Subject(s)
Aging , Cognition Disorders/diagnosis , Culture , Hispanic or Latino , Neuropsychological Tests , Prejudice , Aged , Female , Humans , Male , New MexicoABSTRACT
Changes in cognitive function were investigated in 566 subjects 65-86 years old at baseline, who are a subsample of the Western Collaborative Group Study, a cardiovascular epidemiologic study of middle-aged men that began in the 1960s. Cognitive function was assessed in 1986-1988 (baseline) and again in 1992-1994 by three standardized measures: the Benton Visual Retention Test, the Controlled Oral Word Association Test, and the Digit Symbol Substitution (DSS) Test. Longitudinal change in performance was defined as the shift over time in a subject's quartile rank ordering, using the baseline distribution of test scores as a standard. 'Decliners' and 'improvers' in cognitive function were subjects who lost or gained, respectively, two or more quartile ranks on all three tests combined. By this definition, 20% (n = 113) of subjects declined, compared with 17% (n = 95) who improved in cognitive performance from 1986-1988 to 1992-1994. After adjustment for age, education, and physical health, decline in cognitive performance was significantly associated with poor self-perceived health ratings, depression scale scores, and self-reports of physical activity. Rank score change in the DSS Test was the single best predictor of cognitive function at follow-up on a diverse battery of neuropsychological tests.