Phthalates and perfluorooctanesulfonic acid in human amniotic fluid: temporal trends and timing of amniocentesis in pregnancy

Background: Measures of prenatal environmental exposures are important, and amniotic fluid levels may directly reflect fetal exposures during hypothesized windows of vulnerability.Objectives: We aimed to detect various phthalate metabolites and perfluorooctanesulfonic acid (PFOS) in human amniotic fluid, to study temporal exposure trends, and to estimate potential associations with gestational week of amniocentesis and maternal age and parity at amniocentesis.Methods: We studied 300 randomly selected second-trimester amniotic fluid samples from a Danish pregnancy-screening biobank covering 1980 through 1996. We used only samples from male offspring pregnancies. We assayed the environmental pollutants by liquid chromatography/triple quadrupole mass spectrometry and analyzed data using generalized linear regression models.Results: We detected the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) at a median concentration of 0.27 ng/mL [interquartile range (IQR): 0.20–0.37 ng/mL], the diisononyl phthalate (DiNP) metabolite mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP) at 0.07 ng/mL (IQR: 0.05–0.11 ng/mL), and PFOS at 1.1 ng/mL (IQR: 0.66–1.60 ng/mL). An increase of 1 calendar year was associated with 3.5% lower [95% confidence interval (CI): –4.8%, –2.1%] 5cx-MEPP levels and with 7.1% higher (95% CI: 5.3%, 9.0%) 7cx-MMeHP levels. For each later gestational week of amniocentesis, 5cx-MEPP was 9.9% higher (95% CI: 4.8%, 15.2%), 7cx-MMeHP was 8.6% higher (95: CI: 2.7%, 14.9%), and PFOS was 9.4% higher (95: CI: 3.3%, 15.9%). We observed no associations with maternal age or parity.Conclusions: Measured metabolite levels appeared to parallel decreasing DEHP exposure and increasing DiNP exposure during the study period. The environmental pollutant levels were positively associated with later gestational age at amniocentesis during pregnancy weeks 12–22.     

Listening to the rural health workers in Papua New Guinea - the social factors that influence their motivation to work

Despite rural health services being situated and integrated within communities in which people work and live, the complex interaction of the social environment on health worker motivation and performance in Low Middle Income Countries has been neglected in research. In this article we investigate how social factors impact on health worker motivation and performance in rural health services in Papua New Guinea (PNG). Face-to-face in-depth interviews were conducted with 33 health workers from three provinces (Central, Madang, and Milne Bay) in PNG between August and November 2009. They included health extension officers, community health workers and nursing officers, some of whom were in charge of the health centres. The health centres were a selection across church based, government and private enterprise health facilities. Qualitative analysis identified the key social factors impacting on health worker motivation and performance to be the local community context, gender roles and family related issues, safety and security and health beliefs and attitudes of patients and community members. Our study identified the importance of strong supportive communities on health worker motivation. These findings have implications for developing sustainable strategies for motivation and performance enhancement of rural health workers in resource poor settings.     

Evaluation of an opa gene-based nucleic acid amplification test for detection of Neisseria gonorrhoeae in urogenital samples in North India

SUMMARY Due to the poor positive predictive value of nucleic acid amplification tests (NAATs) for gonorrhoea when applied to a low-prevalence setting, current guidelines recommend the use of supplementary polymerase chain reaction (PCR) targeting a different gene for confirmation of true positives in urogenital specimens. This study sought to standardize and evaluate performance of an in-house opa gene-based PCR assay for gonorrhoea compared to assays targeting the porA pseudogene and 16S rRNA gene. Four hundred samples (300 endocervical, 100 urethral swabs) from patients attending STD clinics in New Delhi, India were used. The sensitivity, specificity, positive predictive value and negative predictive value of the opa-based PCR were 100%, 97·9%, 89·5% and 100%, respectively. In females, the use of NAATs provided enhanced diagnosis of gonorrhoea.     

Oral Delivery of Bioencapsulated Proteins Across Blood–Brain and Blood–Retinal Barriers

Delivering neurotherapeutics to target brain-associated diseases is a major challenge. Therefore, we investigated oral delivery of green fluorescence protein (GFP) or myelin basic protein (MBP) fused with the transmucosal carrier cholera toxin B subunit (CTB), expressed in chloroplasts (bioencapsulated within plant cells) to the brain and retinae of triple transgenic Alzheimer''s disease (3×TgAD) mice, across the blood–brain barriers (BBB) and blood–retinal barriers (BRB). Human neuroblastoma cells internalized GFP when incubated with CTB-GFP but not with GFP alone. Oral delivery of CTB-MBP in healthy and 3×TgAD mice shows increased MBP levels in different regions of the brain, crossing intact BBB. Thioflavin S–stained amyloid plaque intensity was reduced up to 60% by CTB-MBP incubation with human AD and 3×TgAD mice brain sections ex vivo. Amyloid loads were reduced in vivo by 70% in hippocampus and cortex brain regions of 3×TgAD mice fed with bioencapsulated CTB-MBP, along with reduction in the ratio of insoluble amyloid β 42 (Aβ₄₂) to soluble fractions. CTB-MBP oral delivery reduced Aβ₄₂ accumulation in retinae and prevented loss of retinal ganglion cells in 3×TgAD mice. Lyophilization of leaves increased CTB-MBP concentration by 17-fold and stabilized it during long-term storage in capsules, facilitating low-cost oral delivery of therapeutic proteins across the BBB and BRB.     

In vivo contrast free chronic myocardial infarction characterization using diffusion-weighted cardiovascular magnetic resonance

Background

Despite the established role of late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in characterizing chronic myocardial infarction (MI), a significant portion of chronic MI patients are contraindicative for the use of contrast agents. One promising alternative contrast free technique is diffusion weighted CMR (dwCMR), which has been shown ex vivo to be sensitive to myocardial fibrosis. We used a recently developed in vivo dwCMR in chronic MI pigs to compare apparent diffusion coefficient (ADC) maps with LGE imaging for infarct characterization.

Methods

In eleven mini pigs, chronic MI was induced by complete occlusion of the left anterior descending artery for 150 minutes. LGE, cine, and dwCMR imaging was performed 8 weeks post MI. ADC maps were derived from three orthogonal diffusion directions (b = 400 s/mm²) and one non-diffusion weighted image. Two semi-automatic infarct classification methods, threshold and full width half max (FWHM), were performed in both LGE and ADC maps. Regional wall motion (RWM) analysis was performed and compared to ADC maps to determine if any observed ADC change was significantly influenced by bulk motion.

Results

ADC of chronic MI territories was significantly increased (threshold: 2.4 ± 0.3 μm²/ms, FWHM: 2.4 ± 0.2 μm²/ms) compared to remote myocardium (1.4 ± 0.3 μm²/ms). RWM was significantly reduced (threshold: 1.0 ± 0.4 mm, FWHM: 0.9 ± 0.4 mm) in infarcted regions delineated by ADC compared to remote myocardium (8.3 ± 0.1 mm). ADC-derived infarct volume and location had excellent agreement with LGE. Both LGE and ADC were in complete agreement when identifying transmural infarcts. Additionally, ADC was able to detect LGE-delineated infarcted segments with high sensitivity, specificity, PPV, and NPV. (threshold: 0.88, 0.93, 0.87, and 0.94, FWHM: 0.98, 0.97, 0.93, and 0.99, respectively).

Conclusions

In vivo diffusion weighted CMR has potential as a contrast free alternative for LGE in characterizing chronic MI.     

The relation of type 2 diabetes and cancer

Increasing evidence indicates that individuals with type 2 diabetes (diabetes) are at elevated risk for several common human malignancies, including cancers of the colon, breast, endometrium, pancreas, and liver. In particular, the consistent positive results reported by prospective investigations make it unlikely that methodologic issues, occult tumors, or chance results could explain the findings. Since diabetes and impaired fasting glucose together affect >25% of Americans above age 50, even a moderate etiologic association (e.g., relative risk = 1.5) would explain >10% of involved malignancies. Laboratory studies have suggested biologically plausible mechanisms. Insulin, for example, is typically at high levels during the development and early stages of diabetes. Activation of the insulin receptor by its ligand, or cross-activation of the insulin-like growth factor-I receptor, has been shown to be mitogenic and promote tumorigenesis in various model systems. A "unifying concept," in fact, holds that hyperinsulinemia may underlie the cancer associations of several additional risk factors, including high waist circumference, visceral fat, waist-to-hip ratio, body mass index, sedentary lifestyle, and energy intake. In this review, we assess current evidence regarding the relation of type 2 diabetes with cancer, and evaluate the findings in terms of well-accepted criteria for establishing causality.     

Effects of rhythm regularization and rate control in improving left ventricular function in atrial fibrillation patients undergoing atrioventricular nodal ablation

OBJECTIVES: To assess the relative contributions of rate control and rhythm regularization to left ventricular function in atrial fibrillation (AF) patients undergoing atrioventricular nodal ablation. This was performed by assessing the effect of ventricular rhythm regularization on left ventricular function during AF, and the effect of varying heart rate on left ventricular function after ablation. PATIENTS AND METHODS: Eleven patients with continuous AF and V/VI-R pacemakers undergoing therapeutic atrioventricular nodal ablation were studied. Preablation patients underwent two 30 min observation periods in a randomized, blinded fashion during which they were either in baseline AF (pacer set to default V/VI 50/min) or being paced using a rhythm stabilizing algorithm (RSA) designed to regularize rhythm without changing baseline ventricular rate. Six weeks after ablation, patients were again observed during the two following 30 min periods: pacing at a low clinically indicated rate (69+/-9 beats/min), and pacing at the rapid, mean preablation rate. During all observation periods, left ventricular function was measured continuously using a nuclear vest that provided validated measures of heart rate, ejection fraction, and normalized end-systolic volume (ESV) and end-diastolic (EDV) volume. RESULTS: Before ablation, RSA successfully regularized rhythm, decreasing the coefficient of variation of interbeat intervals 20+/-5% to 10+/-4% (P<0.001). The heart rate with RSA (105+/-19 beats/min) was not significantly different from the baseline AF rate (102+/-21 beats/min). Increased rhythm regularity achieved by RSA significantly improved left ventricular function, decreasing ESV from 62+/-12 units to 57+/-11 units (P=0.03), and increasing the ejection fraction from 31+/-11% to 36+/-11% (P=0.03). After ablation, at the clinically indicated low pacing rate of 69+/-9 beats/min, a much greater improvement in ejection fraction was observed, increasing to 44+/-13% (P=0.005 compared with preablation). However, rapid regular pacing at the mean preablation rate of 110+/-18 beats/min eradicated this improvement, decreasing the ejection fraction to 31+/-8% (P=0.003), and increasing ESV from 53+/-13 units to 62+/-8 units (P=0.006). CONCLUSIONS: Rhythm regularity achieved by a regularizing pacing algorithm can significantly, albeit modestly, improve left ventricular function in AF. However, more marked improvements in left ventricular function seen after ablation are primarily due to rate reduction alone.     

Total insulinlike growth factor 1 and insulinlike growth factor binding protein levels, functional status, and mortality in older adults

OBJECTIVES: To assess the association between total insulinlike growth factor (IGF)‐1, IGF binding protein‐1 (IGFBP‐1), and IGFBP‐3 levels and functioning and mortality in older adults. DESIGN: Cohort study. SETTING/PARTICIPANTS: One thousand one hundred twenty‐two individuals aged 65 and older without prior cardiovascular disease events participating in the Cardiovascular Health Study. MEASUREMENTS: Baseline fasting plasma levels of IGF‐1, IGFBP‐1, and IGFBP‐3 (defined as tertiles, T1‐T3) were examined in relationship to handgrip strength, time to walk 15 feet, development of new difficulties with activities of daily living (ADLs), and mortality. RESULTS: Higher IGFBP‐1 predicted worse handgrip strength (P‐trend_T1‐T3<.01) and slower walking speed (P‐trend_T1‐T3=.03), lower IGF‐1 had a borderline significant association with worse handgrip strength (P‐trend_T1‐T3=.06), and better grip strength was observed in the middle IGFBP‐3 tertile than in the low or high tertiles (P=.03). Adjusted for age, sex, and race, high IGFBP‐1 predicted greater mortality (P‐trend_T1‐T3<.001, hazard ratio (HR)_T3vsT1=1.48, 95% confidence interval (CI)=1.15–1.90); this association was borderline significant after additional confounder adjustment (P‐trend_T1‐T3=.05, HR_T3vsT1=1.35, 95% CI=0.98–1.87). High IGFBP‐1 was associated with greater risk of incident ADL difficulties after adjustment for age, sex, race, and other confounders (P‐trend_T1‐T3=.04, HR_T3vsT1=1.40, CI=1.01–1.94). Neither IGF‐1 nor IGFBP‐3 level predicted mortality or incident ADL difficulties. CONCLUSION: In adults aged 65 and older, high IGFBP‐1 levels were associated with greater risk of mortality and poorer functional ability, whereas IGF‐1 and IGFBP‐3 had little association with these outcomes.     

Leishmania donovani in blood smears of asymptomatic persons

Leishmania amastigotes have been detected in the peripheral blood smears of Indian kala-azar patients mostly during night. It was, therefore, thought worthwhile to find out whether such amastigotes could be shown in healthy subjects who did not have any symptoms by history or signs on clinical examination. Leishmania-stained blood smears of 450 asymptomatic healthy individuals residing in an endemic village in Bihar (India) were examined by oil-immersion microscopy for the detection of amastigote, six people (1.3%) showed the presence of Leishmania amastigotes. Given the low sensitivity of a single smear examination it is likely that a much greater proportion of asymptomatic persons had parasitemia than the observed 1.3%. This finding is important from the point of view of transmission of disease, as also for modifying the current control measures.