The Associations Between Serum Insulin-like Growth Factor-I, Brain White Matter Volumes, and Cognition in Mild Cognitive Impairment and Alzheimer's Disease.

Background: Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer's disease (AD). Objective: To explore whether serum IGF-I is associated with magnetic resonance imaging - estimated brain white matter volumes or cognitive functions. Methods: In a prospective study of SCI/MCI (n = 106) and AD (n = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and Stroop tests I-III at baseline, and after 2 years. Results: IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables. Conclusions: Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain.

Low Serum Insulin-like Growth Factor-I Is Associated with Decline in Hippocampal Volume in Stable Mild Cognitive Impairment but not in Alzheimer's Disease.

BACKGROUND: Serum insulin-like growth factor-I (IGF-I) has shown some association with hippocampal volume in healthy subjects, but this relation has not been investigated in stable mild cognitive impairment (sMCI) or Alzheimer's disease (AD). OBJECTIVE: At a single memory clinic, we investigated whether serum IGF-I was associated with baseline magnetic resonance imaging (MRI)-estimated brain volumes and longitudinal alterations, defined as annualized changes, up to 6 years of follow-up. METHODS: A prospective study of patients with sMCI (n = 110) and AD (n = 60). Brain regions included the hippocampus and amygdala as well as the temporal, parietal, frontal, and occipital lobes, respectively. RESULTS: Serum IGF-I was statistically similar in sMCI and AD patients (112 versus 123 ng/mL, p = 0.31). In sMCI, serum IGF-I correlated positively with all baseline MRI variables except for the occipital lobe, and there was also a positive correlation between serum IGF-I and the annualized change in hippocampal volume (rs = 0.32, p = 0.02). Furthermore, sMCI patients having serum IGF-I above the median had lower annual loss of hippocampal volume than those with IGF-I below the median (p = 0.02). In contrast, in AD patients, IGF-I did not associate with baseline levels or annualized changes in brain volumes. CONCLUSION: In sMCI patients, our results suggest that IGF-I exerted neuroprotective effects on the brain, thereby maintaining hippocampal volume. In AD, serum IGF-I did not associate with brain volumes, indicating that IGF-I could not induce neuroprotection in this disease. This supports the notion of IGF-I resistance in AD.

Higher thyroid function is associated with accelerated hippocampal volume loss in Alzheimer's disease.

BACKGROUND: In epidemiological studies, higher thyroid hormone (TH) levels have been associated with lower brain volume and increased risk of Alzheimer's disease (AD) in elderly individuals. However, the relationships between serum THs and hippocampal atrophy rates have previously not been investigated. METHODS: A prospective study of patients with AD (n = 55), stable mild cognitive impairment (sMCI; n = 84) and healthy controls (n = 29) recruited at a single memory clinic. We investigated whether serum THs were associated with magnetic resonance imaging (MRI)-estimated hippocampal volumes at baseline and with longitudinal alterations, defined as annualized percent changes. RESULTS: Serum levels of free triiodothyronine (FT3) and FT3/free thyroxine (FT4) ratio were reduced in AD and sMCI patients compared with the controls (p < 0.05). Hierarchical linear regression analyses showed that higher serum FT3/FT4 ratio was associated with greater baseline hippocampal volume in all study groups. Only in AD patients, higher serum FT4 was associated with lower baseline volume of the left hippocampus. Finally, exclusively in the AD group, higher serum levels of FT3 and FT3/FT4 ratio, and lower serum TSH levels, were associated with greater annual hippocampal volume loss. CONCLUSIONS: In all study groups, FT3/FT4 ratio was related to baseline hippocampal volume. However, only in AD patients, higher levels of THs were associated with greater annual loss of hippocampal volume, suggesting that excessive TH levels exert a deleterious effect on the hippocampus in the presence of existing AD neuropathology.

Altered thyroid hormone profile in patients with Alzheimer's disease.

BACKGROUND: Epidemiological studies have linked higher levels of thyroid hormones (THs) to increased risk of Alzheimer's disease (AD), whereas in advanced AD, THs have been unchanged or even decreased. In early AD dementia, little is known whether THs are related to AD neuropathology or brain morphology. METHODS: This was a cross-sectional study of 36 euthyroid AD patients and 34 healthy controls recruited at a single memory clinic. Levels of THs were measured in serum and cerebrospinal fluid (CSF). In addition, we determined AD biomarkers (amyloid-ß1-42, total tau and phosphorylated tau) in CSF and hippocampal and amygdalar volumes using magnetic resonance imaging. RESULTS: Serum free thyroxine (FT4) levels were elevated, whereas serum free triiodothyronine (FT3)/FT4 and total T3 (TT3)/total T4 (TT4) ratios were decreased, in AD patients compared to controls. In addition, serum TT4 was marginally higher in AD (p = 0.05 vs. the controls). Other TH levels in serum as well as CSF concentrations of THs were similar in both groups, and there were no correlations between THs and CSF AD biomarkers. However, serum FT3 correlated positively with left amygdalar volume in AD patients and serum TT3 correlated positively with left and right hippocampal volume in controls. CONCLUSIONS: Thyroid hormones were moderately altered in mild AD dementia with increased serum FT4, and in addition, the reduced T3/T4 ratios may suggest decreased peripheral conversion of T4 to T3. Furthermore, serum T3 levels were related to brain structures involved in AD development.

Patients with Alzheimer's Disease Have Increased Levels of Insulin-like Growth Factor-I in Serum but not in Cerebrospinal Fluid.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is important for amyloid-ß (Aß) metabolism, and also interacts with the brain vasculature. In previous IGF-I studies, it has not been evaluated whether Alzheimer's disease (AD) patients had vascular comorbidities. OBJECTIVE AND METHODS: A cross-sectional study of 40 consecutive non-diabetic AD patients and 36 healthy controls. We measured IGF-I in serum and cerebrospinal fluid (CSF) and also serum insulin. Mixed forms of AD and vascular dementia were excluded. RESULTS: After adjustment for covariates including age, serum IGF-I level was higher in the AD group than in the controls, whereas CSF IGF-I and serum insulin were unchanged. Binary logistic regression confirmed that high serum IGF-I was associated with increased prevalence of AD [adjusted Odds Ratio (OR) = 1.83, 95% confidence interval (CI): 1.005-3.32 per standard deviation (SD) increase in serum IGF-I]. This association was more robust after exclusion of patients receiving treatment with acetylcholinesterase inhibitors or N-methyl D-aspartate (NMDA) receptor antagonists (OR = 2.23, 95 % CI: 1.10-4.48). In the total study population (n = 76) as well in the AD group (n = 40), serum IGF-I correlated negatively with CSF Aß1-42, and CSF IGF-I correlated positively with CSF/serum albumin ratio, CSF total tau, and CSF phosphorylated tau. CONCLUSION: In AD patients without major brain vascular comorbidities, serum but not CSF levels of IGF-I were increased after correction for covariates. This association was strengthened by exclusion of patients receiving medical treatment. Overall, the results support the notion of IGF-I resistance in mild AD dementia.

Low serum concentration of free triiodothyronine (FT3) is associated with increased risk of Alzheimer's disease.

BACKGROUND: In epidemiological studies, thyroid hormones (THs) have been associated with the risk of dementia. However, little is known of the relation between THs and risk of Alzheimer's disease (AD) or vascular dementia (VaD) in a memory clinic population. METHODS: In a mono-center study, serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were assessed in 302 patients. All patients had subjective or objective mild cognitive impairment and none received treatment with THs. Cox proportional hazards regression analyses was used to determine whether THs at baseline were associated with the risk of conversion to all-cause dementia, AD or VaD. RESULTS: During the follow-up (mean 2.8 years), 82 (28%) of the patients progressed to dementia [AD, n = 55 (18%) and VaD, n = 17 (6%)]. Serum concentrations of TSH, FT4, and FT3 did not associate with all-cause dementia or VaD. Higher serum FT3 was associated with lower risk of conversion to AD [hazard ratio (HR) = 054; 95% confidence interval (CI): 0.32-0.92 per 1 pmol/L increase]. Furthermore, patients in the lowest serum FT3 quartile had a twofold increased risk of AD compared to those in the highest quartile (HR = 2.63; 95% CI: 1.06-6.47). These associations remained after adjustment for multiple covariates. CONCLUSIONS: In a memory clinic population, there was an inverse, linear association between serum FT3 and risk of AD whereas THs did not associate with all-cause dementia or VaD. Further studies are needed to determine the underlying mechanisms as well as the clinical significance of these findings.

Low serum insulin-like growth factor-I (IGF-I) level is associated with increased risk of vascular dementia.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is important for the adult brain, but little is known of the role of IGF-I in Alzheimers disease (AD) or vascular dementia (VaD). METHODS: A prospective study of 342 patients with subjective or objective mild cognitive impairment recruited at a single memory clinic. We determined whether serum IGF-I concentrations at baseline were associated with the risk of all-cause dementia, AD, or VaD. Patients developing mixed forms of AD and VaD were defined as suffering from VaD. The statistical analyses included Cox proportional hazards regression analysis. RESULTS: During the follow-up (mean 3.6 years), 95 (28%) of the patients developed all-cause dementia [AD, n=37 (11%) and VaD, n=42 (12%)]. Low as well as high serum IGF-I (quartile 1 or 4 vs. quartiles 2-3) did not associate with all-cause dementia [crude hazard ratio (HR) 1.30, 95% confidence interval (CI): 0.81-2.08 and crude HR 1.05, 95% CI: 0.63-1.75, respectively] or AD (crude HR 0.79, 95% CI: 0.35-1.79 and crude HR 0.94, 95% CI: 0.43-2.06, respectively]. In contrast, low serum IGF-I concentrations were associated with increased risk of VaD (quartile 1 vs. quartiles 2-3, crude HR 2.22, 95% CI: 1.13-4.36). The latter association remained significant also after adjustment for multiple covariates. CONCLUSIONS: In a memory clinic population, low serum IGF-I was a risk marker for subsequent VaD whereas low IGF-I did not associate with the risk of AD. High serum IGF-I was not related to the risk of conversion to dementia.

Application of the central composite design to study the flocculation of an anionic azo dye using quaternized cellulose nanofibrils.

Cellulose nanofibrils (CNF) grafted with glycidyltrimethylammonium chloride (GTMAC), containing quaternary ammonium contents of 0.44 (QCNF-1), 1.47 (QCNF-2), and 2.28 (QCNF-3) meqg(-1), were evaluated as flocculants for the removal of Reactive Orange 16, an anionic azo dye, from aqueous solution. A rotatable and orthogonal central composite design was used to examine the performance of QCNFs under a range of experimental conditions. Removal efficiencies at the centre point of the design space were found to be 236.9±7.8, 254.2±3.8, and 264.6±2.8mgg(-1) for QCNF-1, QCNF-2 and QCNF-3, respectively. The highest removal efficiency, 295.1mgg(-1), was observed when using QCNF-3 at a low monovalent salt concentration. The QCNF reported herein provides a sustainable and biodegradable alternative to traditional synthetic flocculants for the decolorization of dye-containing effluents.

Stigma and Burden Among Relatives of Persons With Schizophrenia: Results From the Swedish COAST Study.

OBJECTIVE: The aim was to apply a structured questionnaire, the Inventory of Stigmatizing Experiences (ISE), to study experiences of stigma (associated stigma) among relatives of persons with schizophrenia who attended outpatient clinics, using an approach based on assertive community treatment in a Swedish major city. A second aim was to explore the relationship between associated stigma and overall burden among these relatives. METHODS: Relatives (N=65) of persons taking oral antipsychotics who attended outpatient clinics completed a mailed questionnaire that included the ISE and the Burden Inventory for Relatives of Persons with Psychotic Disturbances. Associations were analyzed with ordinal logistic regression. RESULTS: More than half of the relatives (53%) stated that their ill relative had been stigmatized, but only 18% (N=11) reported that they themselves had been stigmatized (responses of sometimes, often, or always). One-fifth of the relatives (23%) acknowledged that they avoided situations that might elicit stigma. Neither experienced stigma nor anticipated stigma was associated with overall burden level in ordinal logistic regression models. The impact of stigma on both the relative's personal quality of life and the family's quality of life were both significantly associated with overall burden after adjustment for patient age and level of functioning. CONCLUSIONS: Stigma had an impact on quality of life at the personal and family levels, and this was associated with overall burden. Increased awareness among service providers may decrease the impact of stigma on relatives, but associations need to be examined in larger studies in diverse cultures and treatment settings.

Stimuli-responsive Pickering emulsions: recent advances and potential applications.

Pickering emulsions possess many advantages over traditional surfactant stabilized emulsions. For example, Pickering emulsions impart better stability against coalescence and, in many cases, are biologically compatible and environmentally friendly. These characteristics open the door for their use in a variety of industries spanning petroleum, food, biomedicine, pharmaceuticals, and cosmetics. Depending on the application, rapid, but controlled stabilization and destabilization of an emulsion may be necessary. As a result, Pickering emulsions with stimuli-responsive properties have, in recent years, received a considerable amounts of attention. This paper provides a concise and comprehensive review of Pickering emulsion systems that possess the ability to respond to an array of external triggers, including pH, temperature, CO2 concentration, light intensity, ionic strength, and magnetic field. Potential applications for which stimuli-responsive Pickering emulsion systems would be of particular value, such as emulsion polymerization, enhanced oil recovery, catalyst recovery, and cosmetics, are discussed.

Stigma, discrimination and medication adherence in schizophrenia: results from the Swedish COAST study.

The aims of this naturalistic non-interventional study were to quantify the level of stigma and discrimination in persons with schizophrenia and to test for potential associations between different types of stigma and adherence to antipsychotics. Antipsychotic medication use was electronically monitored with a Medication Event Monitoring System (MEMS®) for 12 months in 111 outpatients with schizophrenia and schizophrenia-like psychosis (DSM-IV). Stigma was assessed at endpoint using the Discrimination and Stigma Scale (DISC). Single DISC items that were most frequently reported included social relationships in making/keeping friends (71%) and in the neighborhood (69%). About half of the patients experienced discrimination by their families, in intimate relationships, regarding employment and by mental health staff. Most patients (88%) wanted to conceal their mental health problems from others; 70% stated that anticipated discrimination resulted in avoidance of close personal relationships. Non-adherence (MEMS® adherence≤0.80) was observed in 30 (27.3%). When DISC subscale scores (SD) were entered in separate regression models, neither experienced nor anticipated stigma was associated with adherence. Our data do not support an association between stigma and non-adherence. Further studies in other settings are needed as experiences of stigma and levels of adherence and their potential associations might vary by a healthcare system or cultural and sociodemographic contexts.

Drug attitude and other predictors of medication adherence in schizophrenia: 12 months of electronic monitoring (MEMS(®)) in the Swedish COAST-study.

The aim was to investigate clinical predictors of adherence to antipsychotics. Medication use was electronically monitored with a Medication Event Monitoring System (MEMS(®)) for 12 months in 112 outpatients with schizophrenia and schizophrenia-like psychosis according to DSM-IV. Symptom burden, insight, psychosocial function (PSP) and side effects were rated at baseline. A comprehensive neuropsychological test battery was administered and a global composite score was calculated. The Drug Attitude Inventory (DAI-10) was filled in. A slightly modified DAI-10 version for informants was distributed as a postal questionnaire. Non-adherence (MEMS(®) adherence ≤0.80) was observed in 27%. In univariate regression models low scores on DAI-10 and DAI-10 informant, higher positive symptom burden, poor function, psychiatric side effects and lack of insight predicted non-adherence. No association was observed with global cognitive function. In multivariate regression models, low patient-rated DAI-10 and PSP scores emerged as predictors of non-adherence. A ROC analysis showed that DAI-10 had a moderate ability to correctly identify non-adherent patients (AUC=0.73, p<0.001). At the most "optimal" cut-off of 4, one-third of the adherent would falsely be identified as non-adherent. A somewhat larger AUC (0.78, p<0.001) was observed when the ROC procedure was applied to the final regression model including DAI-10 and PSP. For the subgroup with informant data, the AUC for the DAI-10 informant version was 0.68 (p=0.021). Non-adherence cannot be properly predicted in the clinical setting on the basis of these instruments alone. The DAI-10 informant questionnaire needs further testing.

Cryptosporidial diarrhea in an immunocompetent adult: role of nitazoxanide.

Diarrhea caused by Cryptosporidium is most commonly seen in patients with HIV or AIDS or other immunocompromised conditions like diabetes mellitus, or patients on a high dose of steroids or immunosuppressants. The organism is a parasite that infects gastrointestinal epithelium, producing potential life-threatening diarrhea in people with AIDS but usually self-limiting diarrhea in immunocompetent hosts. Here in, we present an interesting case of persistent diarrhea caused by Cryptosporidium in an immunocompetent adult requiring treatment with nitazoxanide.

Thyroid hormones are associated with poorer cognition in mild cognitive impairment.

BACKGROUND: Alterations in interrelated endocrine axes may be related to the pathogenesis of mild cognitive impairment (MCI) and dementia. METHODS: Salivary cortisol before and after a 0.5-mg dexamethasone test, and serum levels of thyroid-stimulating hormone, total thyroxine (T(4)), free T(4), total triiodothyronine (TT(3)), estradiol, testosterone and insulin-like growth factor 1 were measured in 43 MCI cases and 26 healthy controls. All participants underwent a comprehensive neuropsychological test battery covering the cognitive domains of speed/attention, memory, visuospatial functions, language and executive functions. RESULTS: The MCI group did not differ in basal levels of endocrine markers compared to controls. Among those with MCI, TT(3) levels were inversely associated with cognitive performance across all domains. After stratifying MCI cases according to TT(3) levels, those with relatively high TT(3) levels showed impairment in memory as well as in visuospatial and executive functions. Those with TT(3) levels at or below the lower boundary of the normal range performed comparably to healthy controls. Other endocrine markers were not related to cognitive performance. CONCLUSIONS: Among those with MCI, TT(3) was associated with a neuropsychological profile typical of prodromal Alzheimer's disease. While the mechanisms remain unclear, optimal levels of thyroid hormone under a compromising condition such as MCI and related neuropathology need reconsideration.

Straight talk new approaches in healthcare. Rebuilding healthcare in Louisiana--a blueprint for the nation. Roundtable discussion.

When Hurricane Katrina struck Louisiana last August, it ravaged the healthcare system, which has since been struggling to cope with day-to-day challenges while also preparing for the future. The The Louisiana Recovery Authority (LRA) has been working to develop a blueprint for an equitable, affordable, high-quality healthcare system that's also equipped to respond to future disasters. In this installment of Straight Talk, representatives from Franciscan Missionaries Of Our Lady Health System, Baton Rouge, and Ochsner Health System, New Orleans, discuss the present and future state of healthcare in Louisiana. Modern Healthcare and PricewaterhouseCoopers present Straight Talk. The session on rebuilding Louisiana was held on June 8, 2006 at Modern Healthcare's Chicago headquarters. Fawn Lopez, publisher of Modern Healthcare, was the moderator.

Efeitos da loçäo de lactato de amônio a 12 por cento versus nenhum tratamento para a terapia da xerodermia plantar / The effects of ammonium lactate 12 per cents lotion versus no therapy in the treatment of dry skin of the heels

Sessenta indivíduos participaram de uma comparaçäo randomizada aberta, uni-cega (mascaramento do avaliador), bilateral e pareada. Alocou-se aleatoriamente uma formulaçäo de loçäo de lactato de amônio a 12 por cento ou nenhum tratameno à regiäo plantar direita ou esquerda. A loçäo foi aplicada duas vezes ao dia durante oito semanas no pé alocado, seguindo-se uma fase de regressäo de quatro semanas, na qual näo se aplicou o tratamento em nenhum dos pés. Os indivíduos apresentavam xerodermia plantar pelo menos moderada, igual em ambos os pés. Os que haviam aplicado medicaçöes com ou sem prescriçäo ou que haviam sido submetidos a debridamento mecânico nas duas semanas anteriores foram excluídos, bem como os que utilizaram retinóides orais no mês anterior ao início do estudo. A eficácia do tratamento näo pôde ser avaliada nos pacientes que utilizaram, durante o estudo, produtos tópicos nos pés que näo a medicaçäo pesquisada. Avaliou-se o efeito do lactato de amônio na pele da regiäo plantar, comparando-se sua eficácia à da ausência de tratamento através do "Overall Dryness Severity Score" (Escore de gravidade da xerodermia), "Physician Global Assessment of Improvement/Worsening" (avaliaçäo geral dos médicos de melhora/piora) e "Physician Preference" (preferência dos médicos). As avaliaçöes foram feitas na semana 0 (antes do tratamento) e nas semanas 1, 2, 4, 8, 10 e 12. O "escore de gravidade de xerodermia" foi avaliado em uma escala de 9 pontos, de 0 (pele normal, sem sinais de xerodermia) a 8 (xerodermia grave). A "avaliaçäo geral dos médicos de melhora/piora" foi feita em todas as consultas, exceto na inicial (Tabela 1). Em todas as consultas, com exceçäo da inicial, o pesquisador avaliou se havia alguma diferença entre os dois tipos de abordagem. Se houvesse diferença, o lado tratado era considerado:ligeiramente melhor, moderadamente melhor ou acentuadamente melhor. Também foram documentados os efeitos adversos e feitos "slides" dos locais avaliados nas semanas 0 (antes do tratamento), na semana 8 (final do tratamento) e 12 (final da regressäo)