Disentangling the effects of age and mild traumatic brain injury on brain network connectivity: A resting state fMRI study.

INTRODUCTION: Cognitive complaints are common shortly after mild traumatic brain injury (mTBI) but may persist up to years. Age-related cognitive decline can worsen these symptoms. However, effects of age on mTBI sequelae have scarcely been investigated. METHODS: Fifty-four mTBI patients (median age: 35 years, range 19-64 years, 67% male) and twenty age- and sex-matched healthy controls were studied using resting state functional magnetic resonance imaging in the sub-acute phase. Independent component analysis was used to identify intrinsic connectivity networks (ICNs). A multivariate approach was adopted to evaluate the effects of age and group on the ICNs in terms of (static) functional network connectivity (FNC), intensities of spatial maps (SMs) and time-course spectral power (TC). RESULTS: We observed significant age-related changes for a) FNC: changes between 10 pairs of ICNs, mostly involving the default mode (DM) and/or the cognitive-control (CC) domains; b) SMs: intensity decrease in clusters across three domains and intensity increase in clusters across two domains, including the CC but not the DM and c) TC: spectral power decrease within the 0-0.15 Hz range and increase within the 0.20-0.25 Hz range for increasing age within networks located in frontal areas, including the anterior DM. Groups only differed for TC within the 0.065-0.10 Hz range in the cerebellar ICN and no age × group interaction effect was found. CONCLUSIONS: We showed robust effects of age on connectivity between and within ICNs that are associated with cognitive functioning. Differences between mTBI patients and controls were only found for activity in the cerebellar network, increasingly recognized to participate in cognition. Our results suggest that to allow for capturing the true effects related to mTBI and its effects on cognitive functioning, age should be included as a covariate in mTBI studies, in addition to age-matching groups.

A facile synthesis of silver nanowires and their evaluation in the mitochondrial membrane potential.

Silver nanowires (AgNWs) with a high-aspect-ratio were successfully synthesized by a green method using Lavandula angustifolia plant extract. The morphology of the AgNWs was evaluated as a function of the concentration of precursor salt and nucleating agent. Furthermore, AgNWs were analyzed in a biological model using rat liver mitochondria by measuring their effect on membrane potential. The scanning electron microscopy (SEM), X-ray diffraction (XRD), and transmission electron microscopy (TEM) techniques structurally characterized the nanowires obtained. Also, ultraviolet-visible spectroscopy (UV-Vis) investigated the optical properties of AgNWs. Structural studies show AgNWs fcc with lengths up to 100 µm and diameters ranging from 60 to 130 nm growing in the [110] orientation. Both the CuSO4 nucleating agent and the centrifugation process are essential for the growth of nanowires. Furthermore, inhibition of mitochondrial membrane potential (MMP) depends on the concentration of the nanowires (NWs), suggesting dissipation of the electron transport chain. In this way, AgNWs can be used as a potential tool to verify biological reactions, such as modulation of metabolic pathways, together with the evaluation of a possible influence of biotic or abiotic factors in organisms.

Type 2 diabetes mellitus metabolic control correlates with the phenotype of human monocytes and monocyte-derived macrophages.

AIMS: Monocytes and macrophages express cell-surface markers indicative of their inflammatory and activation status. In this study, we investigated whether these markers are affected or correlated in non-obese T2D subjects, or glycemic/metabolic control variables. METHODS: Clinical data was recorded, and peripheral blood drawn from T2D patients (n = 28) and control subjects (n = 27). Isolated monocytes were evaluated by flow cytometry for the expression of CD14, CD16, and the phenotypic markers for the different states of activation spectrum, such as pro-inflammatory (M1) (HLA-DR, CD86), anti-inflammatory/pro-resolving (M2) (CD163, CD206, MERTK, PD-L1) and metabolically-activated (MMe) (CD36, ABCA-1). From a subset of individuals, monocytes-derived macrophages (MDM) were obtained and evaluated for phenotypic markers. A correlation analysis was performed between the clinical variables and the marker expression. RESULTS: The frequency of CD14++CD16- monocytes was lower in T2D patients and it correlates negatively with poor control in glycemic and metabolic variables. T2D monocytes expressed lower levels of HLA-DR, CD86, PD-L1, and CD163, which correlated negatively with poor metabolic control. In MDM from T2D patients, HLA-DR, CD86 and CD163 expression was lower and it inversely correlated with deficient glycemic or metabolic control parameters. CONCLUSION: The glycemic/metabolic control associated with T2D influences monocyte and MDM phenotypes toward an immune-suppressive phenotype.

Determinants of blood lead levels across the menopausal transition.

In this study, the authors sought to evaluate the impact of menopause on lead remobilization from bone-lead stores. The study was conducted between 1993 and 1995 in Mexico City and included 903 women (mean age = 46.8 y [standard deviation = 8.2 y]). Participants provided information about reproductive variables and known risk factors for high PbB levels. PbB levels were determined with graphite furnace atomic absorption spectrophotometry. The authors used linear-regression models to describe the relationship between PbB levels and variables of interest. PbB levels ranged from 1.0 microg/dl to 43.8 microg/dl (mean = 11.0 microg/dl). Menopausal women at baseline had the highest PbB levels; the mean difference between pre- and postmenopausal women was 0.76 microg/dl (95% confidence interval = 0.024, 1.48). We observed an inverted U-shaped relationship between PbB level and age. The highest PbB levels were observed in women aged 47-50 y. Other important predictors of PbB levels were use of lead-glazed ceramics, number of pregnancies, history of cigarette smoking, and height. Our results support the hypothesis that bone lead may be mobilized during menopause and may constitute an important source of exposure.

Biological monitoring of exposure to sevoflurane in operating room personnel by the measurement of hexafluoroisopropanol and fluoride in urine.

The objectives of this study were to evaluate the value of urinary hexafluoroisopropanol (HFIP) and fluoride (F(-)) measurement for the biological monitoring of operating room personnel exposed to sevoflurane. Fifty members of operating room staffs from eight different hospitals took part in the study. To assess external exposure to sevoflurane, air samples were collected during the whole anaesthesia period by a passive sampling device (3M 3500 organic vapour monitor) attached close to the breathing zone of each subject. Urine was collected before (BA) and at the end of anaesthesia (EA) for the determination of HFIP, fluoride and creatinine. Average airborne concentration of sevoflurane was 19.0 ppm (range: ND-139.9 ppm) with a mean duration of anaesthesia of 221 min (range: 60-435 min). There was a better correlation between external and internal exposure as estimated by EA urinary HFIP (r = 0.78; p <0.0001) compared with EA urinary F(-) (r = 0.41; p = 0.0031). Furthermore determination of urinary HFIP seemed more suited than that of F(-) for the assessment of sevoflurane exposure because of lower background in BA samples (86 % of BA HFIP values were under the limit of detection). Based on these results, values of 9.6 and 4.3 mg HFIP g(-1) creatinine correspond to airborne concentrations of 50 and 20 ppm of sevoflurane, respectively. Among the confounding parameters investigated (body mass index (BMI), sex, cytochrome P450 polymorphism) only BMI showed statistically significant influence on sevoflurane metabolism at these low levels of exposure. The measurement of HFIP in urine at the end of the surgical procedure constitutes a good index to assess occupational exposure to sevoflurane. Further studies will be necessary to propose an health-based limit value which remains to be determined from the relationship between effects and internal dose as can be assessed by HFIP measurement in urine.

[Incidence and progression of diabetic retinopathy in low income population of Mexico City]. / Incidencia y progresión de la retinopatía diabética en población de nivel socioeconómico bajo de la Ciudad de México.

Diabetic retinopathy is one of the leading causes of preventable blindness in working age population. Diabetes mellitus and this microvascular complication affects frequently Mexican population and presents itself in severe clinical forms. There are no incidence studies of diabetic retinopathy in Mexico. The four year incidence and progression of diabetic retinopathy were investigated in low income diabetic patients of Mexico City. In the follow up phase we studied 164 patients, 76.6% of the patients studied at baseline, 63 were men and 101 women. All participants had a complete ophthalmological exam and seven field stereo photographs. All photographs were graded using internationally accepted criteria in the reading center of our institution. The four year incidence of any level of retinopathy was 22.5%. Worsening of retinopathy occurred in 20.6% and the proliferative diabetic retinopathy stage was reached in 4.5%. Incidence of diabetic retinopathy was associated to age at diagnosis of diabetes mellitus of less than 45 years and progression was associated to duration of disease of more than ten years. The four year incidence of macular edema was 8.8%. These data are important to plan strategies for prevention of blindness and the implementation of optimal care of diabetic patients in our country.

Moderate-to-severe diabetic retinopathy is more prevalent in Mexico City than in San Antonio, Texas.

OBJECTIVE: To compare the prevalence of diabetic retinopathy (DR) between low-income Mexicans from Mexico City and Mexican-Americans from San Antonio, Texas. RESEARCH DESIGN AND METHODS: We designed a cross-sectional population-based study in low-income neighborhoods of Mexico City and San Antonio. The men and non-pregnant women included in the study had NIDDM and were between 35 and 64 years of age. Ophthalmologic evaluation was performed in 414 patients, 204 in San Antonio and 210 in Mexico City. Seven field standard stereophotographs of each eye were obtained, adapting the Early Treatment Diabetic Retinopathy Study protocol, and graded at the Fundus Photograph Reading Center of the University of Wisconsin. RESULTS: Early nonproliferative DR occurred in 37 (17.6%) and 39 (19.1%) patients in Mexico City and San Antonio, respectively. Moderate-to-severe nonproliferative DR occurred in 55 (26.2%) and 37 (18.1%) patients in Mexico City and San Antonio, respectively, and proliferative DR occurred in 12 (5.7%) and 7 (3.4%) patients in Mexico City and San Antonio, respectively. Using univariate and multivariate logistic regression analysis with DR as the dependent variable, age, duration of disease, and fasting glucose concentration were positively and significantly associated with retinopathy, whereas city, systolic blood pressure, and other selected metabolic variables were not. We defined moderate-to-severe DR to include the categories of moderate-to-severe nonproliferative and proliferative DR. For this combined category, Mexico City patients with diabetes had a significantly higher prevalence (P < 0.01) than those from San Antonio when analyzed by multiple logistic regression analysis (odds ratio for Mexico City/San Antonio, 1.72; 95% CI 1.10-2.70). CONCLUSIONS: Overall prevalence of DR is similar in both cities. However, moderate-to-severe DR is significantly higher in Mexico City.

A diabetic retinopathy screening program as a strategy for blindness prevention.

The most frequent cause of preventable blindness in adults, in the developed world, is diabetic retinopathy (DR). The early treatable phase of this complication is clinically silent. In order to institute effective laser photocoagulation and prevention of blindness, timely detection is crucial. Consequently there is a need for periodic funduscopic examinations of all diabetics. Due to the high prevalence of DM in Mexico most of the primary care facilities are limited. We present the results of a DR screening program (DRSP) using a mobile unit equipped with a fundus photography camera, parked outside of a clinic. We report the prevalence of the various stages of DR and clinical characteristics observed in this population as well as our experience working in such an environment. The study period was from September 1 to December 22, 1995. All the diabetics that presented for care to the clinic were identified and all other persons were invited to participate. A total of 231 participants were invited (112 men, 119 women). Non-stereo fundus photos of two retinal fields (macula and optic disk centered) were taken with technique and classification according to international standards. Response rate to the invitation was 95.3%. Mean age was 62.4 +/- 13 years and 63.5 +/- 10 years and duration of diabetes was 12.3 +/- 10.1 years and 11.0 +/- 7.5 years for men and women, respectively. DR was detected in 38% of the cases, of these only 5.6% have received treatment. DR was uncovered in 84.5% of the cases and was associated with duration of diabetes (p < 0.001 in men and p = 0.04 in women) and hyperglycemia (in men p < 0.005, only). DR has a high prevalence in this population and can be detected through a screening program which reveals undiagnosed high risk DR in an efficient, and standardized manner.

High prevalence of cholelithiasis in a low income Mexican population: an ultrasonographic survey.

The authors present the results of a population-based survey of cholelithiasis carried out in a low-income area of Mexico City using high-resolution gallbladder ultrasound. The purpose of the study was to estimate the prevalence and selected associated risk factors of cholelithiasis (CL). The population of the studied area was 15,532 subjects, of whom 3,505 (22.6%) were eligible for the baseline survey (men and non-pregnant women between 35-64 years of age). Of this group, 1,735 (76.03%, 702 men and 1,033 women) were located for a follow-up study. Ultrasonography was performed on all except for 100 subjects who had undergone previous cholecystectomy. Crude prevalence of CL was 14.1% (95% CI 12.5-15.5). The prevalence was 5.8% (95% CI 4.1-7.5) in men and 19.7% (95% CI 17.3-22.1) in women. Presence of gallstones was associated with age, sex (men p<0.006, women p<0.001), and multiparity (p<0.002). Centrality index in men and body mass index in women were positive and significantly associated with CL when compared with subjects without CL. High levels of fasting and post-glucose load insulin in women and men respectively were associated with CL. The authors conclude that the population of this study has a high prevalence of CL and confirm some known risk factors such as age, sex, BMI and multiparity. Proper assessment of the magnitude problem and characterization of potentially modifiable risk factors will play a major role in preventing this pathology.

Nephropathy in low income diabetics: the Mexico City Diabetes Study.

Among the most serious complications associated with diabetes mellitus (DM) is nephropathy (DN). In Mexico, there is little information on the frequency and clinical characteristics of DN in the Mexican population. We present results of a population-based survey designed to estimate the prevalence of DN. The low income population consisted of 15,532 inhabitants. All 35- to 64-year-old males and non-pregnant women residing in the survey area were identified as eligible for the study (3505; 22.6%). A home interview was obtained in 2810 (80.2%). A physical exam with oral glucose tolerance test was obtained in 2282 (81.2% of those interviewed). DM was diagnosed in 304 (crude rate 13.3%). Mean age for men and women with DM was 51.6 +/- 8.4 and 52.2 +/- 7.5, respectively. Duration of DM in men was 9.2 +/- 8.1 and in women, 7.3 +/- 6.7 years. Hypertension was diagnosed in 19.8% of men and 18.1% of women. Diabetic retinopathy of any level was found in 55.4% of men and 45.7% of women. Mean glycohemoglobin in men was 9.6 +/- 2.1 and in women 9.5 +/- 2.2% (normal 4-8%). At baseline, proteinuria (1+ or more, by dipstick) was found in 24.7% of men and 9.6% of women, microalbuminuria (MA) in 84.4% of men and 63.8% of women. Quantitative albuminuria was abnormally high in 54.7% of men and 40.3% of women. In the 203 diabetics studied with 24 h urine collection for creatinine clearance, normal renal function was found in 69.1% of men and 47.5% of women, reduced renal function was found in 26% of men and 50% of women, renal insufficiency was diagnosed in 4.9% of men and 1.6% of women. One patient was on dialysis and in a subsequent follow up, we found that 2.3% of the patients had died of renal failure, six men (46-63 years) and a woman of 62 years. We conclude that DN is a very serious threat to this population. The high case fatality rate associated with this condition maintains a low prevalence. It is important to develop a program to diminish the frequency of this condition.

Prevalence of gallbladder disease and associated clinical variables in a low income population of Mexico City.

We present the results of a population-based survey carried out in a low income area of Mexico City. The aim of this study is to characterize the prevalence of clinically significant gallbladder disease (CSGD) using the self-reported history of cholecystectomy (CG) or cholelithiasis (CL) demonstrated by cholecystography and/or ultrasonography. The population of the studied area was 15,532 inhabitants, of whom 3505 (22.6%) were age eligible (35-64 year-old men and non-pregnant women). Home interviews were obtained in 2810 (80.2%). A physical and laboratory examination was performed in 2282 individuals (65.1%; 941 men and 1341 women). The prevalence of CSGD in men was 2.0% (95% confidence intervals 1.1-2.9%) and 9.2% in women (95% confidence intervals 7.7-10.7%). Patients with CSGD were older, men (p < 0.003) and women (p < 0.001). Women with CSGD had higher waist to hip circumference ratio (p < 0.06), higher fasting glucose (p < 0.03) as well as 2 h post challenge glycemia (p < 0.04) and insulinemia (p < 0.03). In the multiple logistic regression model only age (p < 0.001) and sex (p < 0.001) remained significantly associated. We conclude that CSGD is quite prevalent in this population. It is associated with age in both genders and in women, higher glucose and insulin levels. The prospective follow-up of this cohort is important since it could generate the information needed to implement a preventive program to diminish the impact of this condition.

Diabetic retinopathy in Mexico. Prevalence and clinical characteristics.

We present the results of a population based study designed to estimate the prevalence of diabetic retinopathy in a series of 284 type 2 diabetics residing in low income areas of Mexico City. These patients were identified in a survey performed between February 1990 and October 1992 (The Mexico City Diabetes Study). We located 214 (75.35%) of the original 284 patients and invited them to attend a clinic where they were interviewed and had a complete ophthalmologic examination. All participants had, in addition to the retinal examination by a certified ophthalmologist, seven fields stereo fundus photographs taken with a Topcon 50X retinal camera. Photos were taken using ASA 100 Kodak film and processed in their laboratory. All photographs were read and graded for quality and level of diabetic retinopathy (DR) in the Reading Center of the Department of Ophthalmology of the University of Wisconsin. A total of 37 (43.5%) men and 69 (53.5%) women had no evidence of DR. In 16 (18.8%) men and 21 (16.3%) women there was background DR. In 25 (29.4%) men and 30 (23.3%) women there was preproliferative DR. In 5 (5.9%) men and in 7 (5.4%) women there was proliferative DR. Macular edema was diagnosed in 7 (8.2%) men and 6 (4.7%) women, of these in 3 (3.5%) men and in 5 (3.9%) women the macular edema was central. This complication is associated with duration of diabetes, chronic poor metabolic control and microalbuminuria. A very significant proportion of cases with sight threatening DR remains undiagnosed and untreated. Consequently there is a significant number of cases developing into blindness that could have been prevented.

Association of sexual activity and bacteriuria in women with non-insulin-dependent diabetes mellitus.

A group of 215 patients with non-insulin-dependent diabetes mellitus (NIDDM) (147 women and 68 men) were selected by home interview, and accepted to undergo clinical examination including urine culture, in order to determine the frequency of bacteriuria and its possible associations with clinical and laboratory findings. Bacteriuria was found in 17.7% of women and 1.5% of men. Univariate and multivariate analysis performed for the group of women revealed sexual intercourse and pyuria as the only factors associated with the frequency of bacteriuria. It was concluded that asymptomatic bacteriuria may be associated with sexual activity in women with NIDDM.