Prechemotherapy Levels of Plasma Dehydroepiandrosterone and Its Sulfated Form as Predictors of Cancer-Related Cognitive Impairment in Patients with Breast Cancer Receiving Chemotherapy.

Study objectiveDehydroepiandrosterone (DHEA) and its sulfated form (DHEAS)-jointly referred to as DHEA(S)-are neurosteroids known to regulate brain development and function that have been found to be positively correlated with cognitive function. It is unknown whether prechemotherapy plasma DHEA(S) levels are associated with the onset of cancer-related cognitive impairment (CRCI). The objective of this study was to evaluate whether an association exists between prechemotherapy plasma DHEA(S) levels and onset of CRCI in patients with breast cancer receiving chemotherapy.DesignMulticenter, prospective cohort study.SettingTwo specialized cancer centers in Singapore.PatientsEighty-one patients with early-stage breast cancer (stages I-III) who had no prior exposure to chemotherapy and/or radiotherapy and were scheduled to receive anthracycline-based or taxane-based chemotherapy treatment with curative intent.Measurements and main resultsPatients completed assessments for self-perceived and objective cognitive function at three time points: prechemotherapy (T1), during chemotherapy (T2), and after chemotherapy (T3). Plasma samples were collected prior to chemotherapy, and DHEA(S) levels were quantified by using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariable logistic regression was used to adjust for clinically important factors and to evaluate the association between prechemotherapy plasma DHEA(S) levels and CRCI. Mean ± SD age was 48.9 ± 9.3 years, with 27.8% of patients experiencing clinically significant cognitive impairment based on global Functional Assessment of Cancer Therapy-Cognitive Function scores. The mean ± SD prechemotherapy plasma DHEAS and DHEA levels were 1.61 ± 0.91 μmol/L and 19.21 ± 13.13 nmol/L, respectively. Prechemotherapy DHEAS levels were found to be associated with impairment in the self-perceived cognitive domains of verbal fluency (adjusted odds ratio [OR] 0.27, 95% confidence interval [CI] 0.08-0.96) and mental acuity (adjusted OR 0.25, 95% CI 0.08-0.74). Conversely, DHEA levels were not associated with impairment in any cognitive subdomains.ConclusionOur findings suggest that patients with higher prechemotherapy DHEAS levels had lower odds of developing self-perceived cognitive impairment. Future studies are required to further investigate the effect of DHEA(S) on specific cognitive domains and to validate our findings in independent cohorts

Associations of pubertal stage and body mass index with cardiometabolic risk in Hong Kong Chinese children: A cross-sectional study

Background: Puberty is associated with a clustering of cardiometabolic risk factors (CMRFs) during adolescence that are manifested in later life. Although anthropometric variables such as body mass index (BMI) can predict cardiometabolic risk in children and adolescents, it is not clear whether there is an interaction between pubertal stage and BMI associated with cardiometabolic risk in this age group. This paper examines the association of pubertal stage and BMI with CMRFs in Hong Kong Chinese children. Methods: A cross-sectional school-based study was conducted among 1985 (95.1%) students aged 6 to 18 years. Fasting lipid profile and plasma glucose, blood pressure, body weight, body height and waist circumference were measured. A self-reported pubertal stage questionnaire was used to assess pubertal stage of participants. Two cardiometabolic risk scores, alpha and beta, were constructed to quantify cardiometabolic risk. Cardiometabolic risk score alpha refers to the sum of z-scores of sex-specific, age-adjusted waist circumference, height-adjusted systolic and diastolic blood pressure, fasting plasma glucose, triglyceride and low-density lipoprotein cholesterol, and minus z-score of sex-specific age-adjusted high-density lipoprotein cholesterol. Cardiometabolic risk score beta includes all components of risk score alpha except waist circumference. Results: The interaction of BMI z-score (ZBMI) and pubertal stage demonstrated a significant increase in variance explained in cardiometabolic risk score alpha in boys (0.5%, p = 0.024) and girls (0.7%, p = 0.006) and in cardiometabolic risk score beta in boys (0.8%, p = 0.030) but not in girls (0.5%, p = 0.051). Conclusions: Pubertal stage has an interaction effect on the association of cardiometabolic risk by BMI in boys and may have a similar but lesser effect in girls.published_or_final_versio

Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases

Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment, from diet to the new nanomaterials as putative risk factors has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies, a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzymes such as neprilysin or insulin degrading enzyme. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action

Engineering of In Vitro 3D Capillary Beds by Self-Directed Angiogenic Sprouting

In recent years, microfluidic systems have been used to study fundamental aspects of angiogenesis through the patterning of single-layered, linear or geometric vascular channels. In vivo, however, capillaries exist in complex, three-dimensional (3D) networks, and angiogenic sprouting occurs with a degree of unpredictability in all x,y,z planes. The ability to generate capillary beds in vitro that can support thick, biological tissues remains a key challenge to the regeneration of vital organs. Here, we report the engineering of 3D capillary beds in an in vitro microfluidic platform that is comprised of a biocompatible collagen I gel supported by a mechanical framework of alginate beads. The engineered vessels have patent lumens, form robust ~1.5 mm capillary networks across the devices, and support the perfusion of 1 µm fluorescent beads through them. In addition, the alginate beads offer a modular method to encapsulate and co-culture cells that either promote angiogenesis or require perfusion for cell viability in engineered tissue constructs. This laboratory-constructed vascular supply may be clinically significant for the engineering of capillary beds and higher order biological tissues in a scalable and modular manner.Singapore-MIT Alliance for Research and Technolog

EDN1 Lys198Asn is Associated with Diabetic Retinopathy in Type 2 Diabetes

Purpose: We tested the hypothesis that genetic variants in vasoactive and angiogenic factors regulating the retina vasculature contribute to the development of diabetic retinopathy (DR). Methods: A case-control study was performed to study the genetic association between DR and polymorphic variants of EDN1 (Lys198Asn), LTA (IVS1–80C>A, IVS1–206G>C, IVS1–252>G), eNOS (Glu298Asp), and ITGA2 (BgI II) in a Chinese population with type 2 diabetes mellitus. A well defined population with type 2 diabetes, consisting of 127 controls and 216 DR patients, was recruited. Results: A higher frequency of the Asn/Asn genotype of EDN1 was found in individuals with at least 10 years of diabetes and no retinopathy (controls) compared with DR patients with any duration of diabetes (DR: 2.3%; control: 11.0%; p=0.0002). The Asn allele was also more frequent in controls than DR patients (DR: 16.4%; control: 29.5%; p=0.007). Multiple logistic regression analysis showed that the Asn/Asn genotype was the factor most significantly associated with reduced risk of DR (odds ratio=0.19; 95% CI: 0.07-0.53; p=0.002) and with late onset of diabetes (Asn/Asn: 59 years; Lys/Lys + Lys/Asn: 53 years; p=0.02). Moreover, the Lys/Lys genotype was more common among patients with nonproliferative (75.7%) than proliferative DR (56.9%; p=0.008). The distributions of Lys198Asn alleles in hypertension did not differ from normotensive subjects. No associations between DR and polymorphisms of LTA, eNOS, or ITGA2 were detected, and there were no detectable gene-gene or gene-environmental interactions among the polymorphisms.Conclusions The Asn/Asn genotype of EDN1 was associated with a reduced risk of DR and with delayed onset of type 2 diabetes

Provision of Clinical Pharmacist Services for Individuals With Chronic Hepatitis C Viral Infection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109934/1/phar1512.pd

Impact of diabetes education and self-management on the quality of care for people with type 1 diabetes mellitus in the Middle East (the International Diabetes Mellitus Practices Study, IDMPS)

Aims: Self-management (self-monitoring of blood glucose, plus self-adjustment of insulin dose) is important in diabetes care, but its complexity presents a barrier to wider implementation, which hinders attainment and maintenance of glycemic targets. More evidence on self-management is needed to increase its implementation and improve metabolic outcomes. Methods: Data from 1316 participants with type 1 diabetes mellitus who were enrolled from Middle East countries into the International Diabetes Management Practices Study (IDMPS), a multinational observational survey, were analyzed to assess the impact of education on disease management and outcomes. Results: A majority (78%) of participants failed to achieve glycemic target (HbA1c < 7.0% [<53 mmol/mol]). Participants who had received diabetes education (59%) were more likely to practice self-management than those who had not (odds ratio [OR]: 2.51; 95% confidence interval [CI]: 1.7–3.69; p < 0.001), and those who practiced self-management were more likely to attain target HbA1c than those who did not (OR: 1.49; 95% CI: 1.06–2.09; p = 0.023).Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Chantelot, Jean Marc. Sanofi; FranciaFil: Domenger, Catherine. Sanofi; FranciaFil: Ramachandran, Ambady. Dr. A. Ramachandran’s Diabetes Hospitals; IndiaFil: Kaddaha, Ghaida. Dubai Health Authority; Emiratos Arabes UnidosFil: Mbanya, Jean Claude. University of Yaounde I; CamerúnFil: Shestakova, Marina. I.M.Sechenov First Moscow State Medical University; RusiaFil: Chan, Juliana. Chinese University of Hong Kong; Hong Kon

Hong Kong Chinese school children with elevated urine melamine levels: A prospective follow up study

<p>Abstract</p> <p>Background</p> <p>In 2008, the outbreak of kidney stones in children fed by melamine-tainted milk products in Mainland China has caused major public concern of food safety. We identified Hong Kong school children with elevated urine melamine level from a community-based school survey in 2007-08 and reviewed their clinical status in 2009.</p> <p>Methods</p> <p>In 2007-08, 2119 school children participated in a primary and secondary school survey in Hong Kong using a cluster sampling method. Urine aliquots from 502 subjects were assayed for melamine level. High urine melamine level was defined as urine melamine/creatinine ratio >7.1 μg/mmol. Subjects with high urine melamine level were invited for clinical evaluation in 2009 including urinalysis and ultrasound imaging of the urinary system.</p> <p>Results</p> <p>The age range of this subcohort was 6 - 20 years with 67% girls (335 female and 167 male subjects). The spot urine melamine/creatinine ratio of the 502 urine aliquots ranged from undetectable to 1467 μg/mmol (median 0.8 μg/mmol). Of these, 213 subjects had undetectable level (42%). We invited 47 (9%) subjects with high urine melamine level for re-evaluation and one subject declined. The median duration of follow-up was 23.5 months (interquartile range: 19.8 - 30.6 months). None of the 46 subjects (28% boys, mean age 13.9 ± 2.9 years) had any abnormality detected on ultrasound study of the urinary system. All subjects had stable renal function with a median urine albumin-creatinine ratio of 0.70 mg/mmol (interquartile range: 0.00 - 2.55 mg/mmol).</p> <p>Conclusions</p> <p>Hong Kong Chinese school children with high urine melamine levels appeared to have benign clinical course in the short term although a long term follow-up study is advisable in those with persistently high urine melamine level.</p