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Nanoelectrodes for measuring intracellular action potentials suffer from issues with success rate, signal strength and fabrication. Here, the authors report on a scalable technique which creates robust nanocrown electrodes with high success rates by electroporation and demonstrate the advance towards preclinical drug evaluation.

Abstract Background The older person is at greater risk of falls due to multiple intrinsic and extrinsic factors. This is compounded when the elderly is admitted to hospitals, as they are acutely ill and placed in an unfamiliar environment. Delirium and polypharmacy further complicate these problems. As falls reflect quality of care with potential for grave outcomes, this study aimed to identify the extent and risk of falls in public hospitals. Methods We conducted a nested case control study in 12 public hospitals in Malaysia. In the cohort section, we screened all inpatients 60 years of age and above daily until discharge, or the end of the study period. Daily, we identified those who fell, inclusive of near falls, in the preceding 24 h. Our enumerators interviewed patients on experience of fall, and supplemented data from the nurses and caregivers. For each case, ten controls were chosen. Results The incidence of falls/near falls was 1.0 per 1000 patient days (95% CI: 0.9, 1.1). Intrinsic risk factors found to be significant included patients who were not from a nursing home or not cared for by a domestic helper prior to admission, had prior history of indoor fall either in home or hospital, had four or more clinical diagnoses or exited from the bed on the weak side. Significant extrinsic factors were the absence of transfer bar in toilet, call bells, light switches or walking aids that were not within reach, as well as not having a walking aid. Non-sturdy chair was associated with lesser falls than when sturdy chairs with armrests were present. Conclusion Querying patients for falls produced better results than incident reporting. Several intrinsic factors such as history of indoor or in-hospital fall, having four or more clinical diagnoses or exiting from weaker side and residence history may help to identify those at higher risk. Addressing significant extrinsic factors such as transfer bars and the identification of switches may help in reducing falls risk in hospitals. Trial registration This study was registered in National Medical Research Register of Malaysia ( NMRR-07-772-1044 ; date 26/05/2008) with Ethics Approval from Medical Research and Ethics Committee (MREC: MRG-07-LOI-HSR-1).

Sporozoite-based approaches currently represent the most effective vaccine strategies for induction of sterile protection against Plasmodium falciparum (Pf) malaria. Clinical development of subunit vaccines is almost exclusively centered on the circum-sporozoite protein (CSP), an abundantly expressed protein on the sporozoite membrane. Anti-CSP antibodies are able to block sporozoite invasion and development in human hepatocytes and subsequently prevent clinical malaria. Here, we have investigated whether sporozoite-induced human antibodies with specificities different from CSP can reduce Pf-liver stage development. IgG preparations were obtained from 12 volunteers inoculated with a protective immunization regime of whole sporozoites under chloroquine prophylaxis. These IgGs were depleted for CSP specificity by affinity chromatography. Recovered non-CSP antibodies were tested for sporozoite membrane binding and for functional inhibition of sporozoite invasion of a human hepatoma cell line and hepatocytes both in vitro and in vivo. Postimmunization IgGs depleted for CS specificity of 9 of 12 donors recognized sporozoite surface antigens. Samples from 5 of 12 donors functionally reduced parasite-liver cell invasion or development using the hepatoma cell line HC-04 and FRG-huHep mice containing human liver cells. The combined data provide clear evidence that non-CSP proteins, as yet undefined, do represent antibody targets for functional immunity against Pf parasites responsible for malaria.

We aimed to investigate the ability of HBsAg plasma level kinetics to predict therapy response by studying 23 children with infancy-acquired chronic hepatitis B ( CHB) during combination sequential therapy with lead-in lamivudine ( LAM) and add-on interferon-α ( IFN-α) [5 responders ( R = anti- HBs seroconversion) and 18 nonresponders ( NR)] and to assess their relationship with pretreatment intrahepatic HBV- DNA and ccc DNA and HBs Ag and HBc Ag liver expression. Plasma HBs Ag levels were measured in samples before (treatment week 0 = TW0), during ( TW9, TW28, TW52) and after (follow-up week = FUW24) therapy by Abbott ARCHITECT® assay [log10 IU/ mL]. Baseline liver HBV- DNA and ccc DNA were quantified by real-time Taq Man PCR [log10copies/ng genomic DNA]. HBs Ag and HBc Ag liver expression was evaluated by immunostaining of formalin-fixed, paraffin-embedded specimens [number of positive cells/1000 hepatocytes]. All results are presented as medians. Plasma: at baseline, on-treatment and during follow-up, HBsAg levels were lower in R than NR ( TW0: 4.36 vs 4.75; TW28: 2.44 vs 4.35; TW52: 0 vs 4.08 and FUW24: 0.17 vs 4.35, all P < 0.05). Liver: baseline HBV- DNA (3.82 vs 4.71, P = 0.16) and ccc DNA (1.98 vs 2.26, P = 0.18) tended to be lower in R than NR, HBs Ag expression was lower in R than NR (0.5 vs 4.7, P = 0.03), and HBc Ag expression was similar between R and NR. There were positive correlations between plasma HBs Ag levels and liver HBV- DNA ( r = 0.44, P = 0.04), ccc DNA ( r = 0.41, P = 0.04) and HBs Ag liver expression ( r = 0.38, P = 0.05). Lower baseline HBs Ag plasma levels, lower HBs Ag expression in liver and on-treatment decline of plasma HBs Ag levels heralds HBs Ag clearance and response to treatment in tolerant children with CHB. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the changes in organic anion-transporting polypeptide 8 (OATP8) expression and enhancement ratio on gadoxetic acid-enhanced MR imaging in hepatocellular nodules during multistep hepatocarcinogenesis.Methods: In imaging analysis, we focused on 71 surgically resected hepatocellular carcinomas (well, moderately and poorly differentiated HCCs) and 1 dysplastic nodule (DN). We examined the enhancement ratio in the hepatobiliary phase of gadoxetic acid enhanced MR imaging [(1/postcontrast T1 value-1/precontrast T1 value)/(1/precontrast T1 value)], then analysed the correlation among the enhancement ratio, tumour differentiation grade and intensity of immunohistochemical OATP8 expression. In pathological analysis, we focused on surgically resected 190 hepatocellular nodules: low-grade DNs, high-grade DNs, early HCCs, well-differentiated, moderately differentiated and poorly differentiated HCCs, including cases without gadoxetic acid-enhanced MR imaging. We evaluated the correlation between the immunohistochemical OATP8 expression and the tumour differentiation grade.Results: The enhancement ratio of HCCs decreased in accordance with the decline in tumour differentiation (P < 0.0001, R = 0.28) and with the decline of OATP8 expression (P < 0.0001, R = 0.81). The immunohistochemical OATP8 expression decreased from low-grade DNs to poorly differentiated HCCs (P < 0.0001, R = 0.15).Conclusions: The immunohistochemical expression of OATP8 significantly decreases during multistep hepatocarcinogenesis, which may explain the decrease in enhancement ratio on gadoxetic acid-enhanced MR imaging. [ABSTRACT FROM AUTHOR]