Nanogold-Based Sensing of Environmental Toxins: Excitement and Challenges

There have been tremendous advances in the past ten years on the development of various nanomaterials-based sensors for detection of environmental toxins. Nanogold is of special interest because of its unique shape- and size-dependent optical properties, hyper-quenching ability, super surface-enhanced Raman and dynamic light scattering, and surface-modifiability by small organic molecules and biomolecules. These unique optical properties of nanogold have been explored for ultra-sensitive detection, while its surface-modifiability has been explored for selectivity. In general, the nanogold-based sensors are highly selective and sensitive along with simple sample preparation and sensor design. In this review article, we intend to capture some of the recent advances in nanogold-based sensor development and mechanistic studies, especially for bacteria, heavy metals, and nitroaromatic compounds. Undoubtedly, these developments will generate a lot of excitement for environmental scientists and toxicologists as well as the general public.     

Image Integration Using Intracardiac Ultrasound and 3D Reconstruction for Scar Mapping and Ablation of Ventricular Tachycardia

Background: Ablation of ventricular tachycardia (VT) reduces implantable cardioverter defibrillator shocks. Intracardiac ultrasound (ICE) can visualize and quantify the function of all left ventricular wall segments. We thus hypothesized that ICE could identify scar tissue and provide a guide to facilitate substrate‐guided VT ablation. Methods: Eighteen patients underwent VT ablation with real time ICE mapping from the right atrium and ventricle with online 3D‐image reconstruction of scar segments. The left ventricle was also scar mapped by traditional electroanatomic mapping (CARTO) for comparison. Images from these 2 scar mapping techniques were compared to each other as well as to a preprocedure transthoracic echocardiogram. Results: The average age was 65 ± 12 years and 12 (67%) were male (15 [83%] had ischemic cardiomyopathy). Two patients (12%) had recurrence of their clinical VT (1 remained on an antiarrhythmic medication, the other had a repeat ablation) over a follow‐up of 127 ± 33 days. No periprocedural or long‐term adverse events occurred. A total of 248 wall segments were analyzed. All 3 modalities were concordant in scar identification in 193 (78%) segments. The ICE segments correlated with the electroanatomic map in 213 (86%) segments versus 198 (80%), which correlated with transthoracic echocardiography and electroanatomic mapping (P = 0.046). Specifically, the ICE wall motion scores were closer to the electroanatomic mapping in the basal segments and showed a higher accuracy in ischemic heart disease. Conclusion: These data demonstrate that real time ICE images provide accurate chamber geometries and scar boundaries of the left ventricle. These scar borders were more accurate than transthoracic echocardiography and illustrate the feasibility of ICE for substrate‐based ablation for VT. (J Cardiovasc Electrophysiol, Vol. 21, pp. 678‐684, June 2010)     

C‐type natriuretic peptide in prostate cancer

C‐type natriuretic peptide (CNP) is expressed in the male reproductive organs in pigs. To examine whether the human prostate also expresses the CNP gene, we measured CNP and N‐terminal proCNP in prostate cancer tissue extracts and performed immunohistochemical biopsy staining. Additionally, proCNP‐derived peptides were quantitated in plasma from patients with prostate cancer. Blood was collected from healthy controls and patients before surgery for localized prostate cancer. Tissue extracts were prepared from tissue biopsies obtained from radical prostatectomy surgery. N‐terminal proCNP, proCNP (1–50) and CNP were measured in plasma and tissue extracts. Biopsies were stained for CNP‐22 and N‐terminal proCNP. Tissue extracts from human prostate cancer contained mostly N‐terminal proCNP [median 5.3 pmol/g tissue (range 1.0–12.9)] and less CNP [0.14 pmol/g tissue (0.01–1.34)]. Immunohistochemistry demonstrated the presence of the peptides in prostatic epithelial cells. The N‐terminal proCNP concentrations in plasma were marginally lower in patients with localized prostate cancer compared with control subjects [13.8 pmol/l (11.0–17.2) vs. 15.1 pmol/l (10.4–23.2), p=0.002] but not enough to justify the use of N‐terminal proCNP as a cancer marker. Further research is needed to establish whether measurement of proCNP‐derived peptides may offer clinical information.     

Prevalence of motor‐skill impairment in preterm children who do not develop cerebral palsy: a systematic review

Aim Motor skill impairment is a common negative outcome in children born preterm who do not develop cerebral palsy (CP). This study aimed to conduct a systematic review of current data to provide an accurate estimate of the prevalence of non‐CP motor impairment in preterm children at school age. Method We searched the Medline, PubMed, and PsycInfo databases and relevant journals to identify all studies published post‐1990 that reported the prevalence of motor impairment in school‐aged children born preterm (<37wks’ gestation) using standardised motor assessment batteries. We applied a range of exclusionary criteria, with 11 studies included in the final analyses. We identified two levels of motor impairment commonly reported – mild–moderate and moderate – and conducted a random effects meta‐analysis to produce a prevalence estimate for each. Results The pooled estimate for mild–moderate impairment in preterm children was 40.5/100. and for moderate motor impairment the estimate was 19.0/100. There was also a trend for lower motor impairment levels in samples born before 1990 compared with those born after 1990. Interpretation Children born preterm are at increased risk of motor impairment, with prevalence three to four times greater than in the general population. This highlights the need for improved surveillance and intervention strategies in this group of children.     

The effect of a basic home stimulation programme on the development of young children infected with HIV

Aims The human immunodeficiency virus (HIV) potentially causes a significant encephalopathy and resultant developmental delay in infected children. The aim of this study was to determine whether a home‐based intervention programme could have an impact on the neurodevelopmental status of children infected with HIV. Method A longitudinal, randomized, controlled trial was conducted. A total of 122 children aged less than 2 years 6 months were assigned to either a comparison or an experimental group. Children in the experimental group were given a home stimulation programme that was updated every 3 months. The home programme included activities to promote motor, cognitive, and speech and language development. Children in the comparison group received no developmental intervention. Children were assessed by a blinded assessor at baseline, 6 months, and 12 months using the Bayley Scales of Infant Development, 2nd edition. Results The children in this study came from poor socioeconomic backgrounds and their nutritional status was suboptimal. The experimental group included 60 children (30 males, 30 females) with a mean age of 18 months (SD 8.1mo). The comparison group included 62 children (32 males, 30 females) with a mean age 19 months (SD 8.2mo). Cognitive and motor development were severely affected at baseline, with 52% of the children having severe cognitive delay and 72% having severe motor delay at baseline. Children in the experimental group showed significantly greater improvement in cognitive (p=0.010) and motor (p=0.020) development over time than children in the comparison group. Interpretation A home stimulation programme taught to the caregiver can significantly improve cognitive and motor development in young children infected with HIV.     

Differential expression of hMLH1 in sporadic human colorectal cancer tumors and distant metastases

Somatic defects in the mismatch repair system constitute an important pathway in colorectal carcinogenesis. We have examined the expression of mismatch repair proteins in sporadic stage IV colorectal tumors and their derived metastases. Sporadic tumors were further examined for differences in expression between the tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver metastases. In cases with loss of mismatch repair protein expression, lymph node metastases were also examined. Clinicopathological parameters and Ki‐67 staining indexes were evaluated and compared. Four tumors displayed a complete loss of hMLH1/hPMS2 expression at the transition zone; however, three of these expressed both proteins at the invasive front and in liver and lymph node metastases. A further four were predominantly hMLH1/hPMS2 negative at the transition zone, but with distinct subclones of hMLH1/hPMS2‐expressing cells at the transition zone. All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No significant difference in the proliferative index was observed for the hMLH1/hPMS2‐compromised group. In stage IV tumors re‐expression of hMLH1/hPMS2 occurred, leading to different patterns of expression within the primary tumor and between tumor and metastases. This may have functional importance for the chemosensitivity of metastases compared to the primary tumor.     

Lipoprotein Alterations and Plasma Lipoprotein Lipase Reduction in Familial Hemophagocytic Lymphohistiocytosis

ABSTRACT. Serum lipid abnormalities are common in familial hemophagocytic lymphohistocytosis (FHL), a disorder also characterized by fever, hepatosplenomegaly, pancytopenia and a prominent lymphohistiocytic accumulation in the mononuclear phagocyte system. The lipoprotein pattern in nine children with FHL was studied with a quantitative method measuring cholesterol and triglycerides in each major class of lipoproteins. Triglycerides were markedly elevated during active FHL in serum, very low density lipoproteins, and low density lipoproteins. Cholesterol was increased in very low density lipoproteins whereas both triglycerides and cholesterol were extremely low in high density lipoproteins. These lipoprotein abnormalities, reversible on successful therapy, are compatible with a depressed lipolytic activity. Post-heparin levels of lipoprotein lipase and hepatic lipase in plasma were studied in four children and found to be markedly low during active FHL. We suggest that inflammatory cytokines, which may strongly suppress lipoprotein lipase activity, can be important mediators in the pathophysiology of FHL and that they may participate in the development of the lipid abnormalities.     

Evaluation of a Transcutaneous Oxygen and Carbon Dioxide Monitor in a Neonatal Intensive Care Department

Transcutaneous-Po₂; (tc-Po₂ (tc-Pco₂) at 44^oC and transcutaneous-Pco₂) at 38, 42, 43 and 44^oC were measured with a currently available monitoring system (TCM222, Radiometer, Copenhagen) in 64 newborn infants with severe respiratory insufficiency during the first five days of life. Tc-Pco₂ at all four temperatures correlated better with arterial blood-Pco₂ (aB-Pco₂)> than tc-Po₂ with aB-Po2. However, the sensitivity and specificity of tc-Po₂ and tc-Pco₂ were similar with regard to maintaining aB-Po₂, and aB-Pco₂ within specified limits. Tc-Pco₂ increased relatively with increasing electrode temperature by a factor which was similar to the anaerobic temperature coefficient of Po₂, in blood. The coefficient of variation of duplicate measurements was 10 % for tc-Po₂ and 5 % for tc-Pco₂. Electrode drift after an average of 3 hours patient monitoring was 2%±6% (1SD) for tc-Pco₂, and -3 %±6 % for tc-Pco₂- We conclude that tc-Po₂ and tc-Pco₂ are a valuable supplement to arterial blood gas measurements, but the variable correlation with arterial blood gas values and the electrode drifts which may occur, mean that they cannot fully replace arterial sampling.