Validation of the Italian version of the Charcot‐Marie‐Tooth disease Pediatric Scale

The Charcot‐Marie‐Tooth disease Pediatric Scale (CMTPedS) is a Rasch‐built clinical outcome measure of disease severity. It is valid, reliable, and responsive to change for children and adolescents aged 3 to 20 years. The aim of this study was to translate and validate an Italian version of the CMTPedS using a validated framework of transcultural adaptation. The CMTPedS (Italian) was translated and culturally adapted from source into Italian by two experts in CMT with good English language proficiency. The two translations were reviewed by a panel of experts in CMT. The agreed provisional version was back translated into English by a professional translator. The definitive Italian version was developed during a consensus teleconference by the same panel. CMT patients were assessed with the final version of the outcome measure and a subset had a second assessment after 2 weeks to evaluate test‐retest reliability. Seventeen patients with CMT aged 5 to 20 years (eight female) were evaluated with the CMTPedS (Italian), and test‐retest was performed in three patients. The CMTPedS (Italian) showed a high test‐retest reliability. No patient had difficulty in completing the scale. The instructions for the different items were clearly understood by clinicians and therefore the administration of the outcome measure was straight forward and easily understood by the children assessed. The CMTPedS (Italian) will be used for clinical follow‐up and in clinical research studies in the Italian population. The data is fully comparable to that obtained from the English language version.     

An adaptation of recombinant vaccinia-based ELISPOT and intracellular cytokine staining for a comparative measurement of cellular immune responses in HIV-1 and HIV-2 infections in West Africa

An efficient and quantitative tool for rapid assessment of human immunodeficiency virus (HIV)-induced cellular immune responses is important for resource-limited settings, such as in sub-Saharan Africa. Modifications are required to previously reported methods for evaluating ex-vivo antigen-specific cellular responses based on direct recombinant vaccinia virus (rVV) stimulation of peripheral blood mononuclear cells (PBMCs) by enzyme linked immunosorbent assay (ELISPOT) and by flow cytometry intracellular cytokine assay (ICA). We made such modifications in order to detect specific responses and compared quantitative cellular immune responses in HIV-1 and HIV-2 infected Gambians. The sensitivity of the rVV-based ELISPOT assay was on average 1.25 interferon (IFN)-gamma spot forming cells (SFC) per 50 000 PBMCs specific for either infection, and 5 IFN-gamma-secreting CD8+ T cells/50 000 in the ICA. The level of IFN-gamma SFC detected by ELISPOT and by ICA were correlated (P < 0.02). ICA detected pol-specific responses in 88% and 67% of HIV-1 and HIV-2 subjects, respectively, and gag-specific responses in more than 80% of both infections. Lower proportions of responders were obtained with ELISPOT, for which pol responses were present in 60% of HIV-1 and 46% of HIV-2 infected patients, and gag responses in 55% and 69%, respectively. The assays did not show any significant difference in cellular immune responses between HIV-1 and HIV-2 infected subjects with CD4% >or= 20%. These outcomes are comparable with results obtained using standard techniques and thus this method is a suitable, rapid and less expensive assessment of cellular immunity.     

Structure–activity investigation of the potentiating effect of cyano substitution on nitroaniline mutagenicity in the ames test

2,6‐Dicyano‐4‐nitroaniline and 2‐cyano‐4‐nitroaniline (CNNA; 2‐amino‐5‐nitrobenzonitrile) are potent mutagens in the Ames test, even though unsubstituted nitroanilines (NAs) are no more than weak mutagens. These compounds are putative reduction products of many commercial azo dyes, including Disperse Blue 165, Disperse Blue 337, Disperse Red 73, Disperse Red 82, Disperse Violet 33, and Disperse Violet 63. We have examined the mutagenicity in strains TA98 and YG1024 of a series of commercially‐available isomers of CNNA, and some related compounds, to probe the relationship between structure and genotoxic activity in this class of compounds. The potentiating effect of the cyano substituent is seen in many cases; e.g. 2‐amino‐4‐nitrobenzonitrile is a much more potent mutagen than 3‐NA. 2,4‐Dinitrobenzonitrile is also highly mutagenic. Possible mechanisms for the “cyano effect” are considered, with respect to the likely structures of cyanonitroaniline‐DNA adducts and the roles of the enzymes (nitroreductase and acetyl CoA:arylamine N‐acetyltransferase) believed to be involved in the activation of nitroaromatic compounds. Environ. Mol. Mutagen. 59:114–122, 2018. © 2017 Wiley Periodicals, Inc.     

Suicide in women with gynecologic cancer

Objective(s)

To characterize the suicide rates among patients with gynecologic cancer in the Unites States and to identify factors associated with high suicide rates.

Method(s)

Subjects with a diagnosis of gynecologic cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) program for the period 1988-2007. Comparison with women in the general US population was based on WHO data 2005, matched for age in 10-year categories. Cox regression models were used to perform multivariate modeling for factors associated with suicide.

Result(s)

Among 252,235 patients followed for 1,207,278 person-years, the suicide rate was 8.3 per 100,000 person-years, with a standardized mortality ratio (SMR) of 1.4 (95% CI 1.2-1.7, p < 0.001). The highest suicide rates were observed in patients with ovarian cancer and within the first year following diagnosis. Suicide risk was associated with younger age at diagnosis, high grade disease and absence of surgical intervention.

Conclusion(s)

Patients with gynecologic cancer have an increased suicide risk when compared to the general population. Suicide rates vary by cancer site and time since diagnosis. Effective screening and appropriate treatment of psychosocial stress among women with gynecologic cancer are warranted.     

Slitrk gene duplication and expression in the developing zebrafish nervous system

Results : As a prelude to examining the functional roles of Slitrks, we identified eight slitrk orthologs in zebrafish and observed that seven of the eight orthologs were actively transcribed in the nervous system at embryonic, larval, and adult stages. Similar to previous findings in mice and humans, zebrafish slitrks exhibited unique but overlapping spatial and temporal expression patterns in the developing brain, retina, and spinal cord. 相似文献   

Mortality and loss to programme before antiretroviral therapy among HIV-infected children eligible for treatment in The Gambia, West Africa

Background

HIV infection among children, particularly those under 24?months of age, is often rapidly progressive; as a result guidelines recommend earlier access to combination antiretroviral therapy (cART) for HIV infected children. Losses to follow-up (LTFU) and death in the interval between diagnosis and initiation of ART profoundly limit this strategy. This study explores correlates of LTFU and death prior to ART initiation among children.

Methods

The study is based on 337 HIV-infected children enrolled into care at an urban centre in The Gambia, including those alive and in care when antiretroviral therapy became available and those who enrolled later. Children were followed until they started ART, died, transferred to another facility, or were LTFU. Cox proportional hazards regression models were used to determine the hazard of death or LTFU according to the baseline characteristics of the children.

Results

Overall, 223 children were assessed as eligible for ART based on their clinical and/or immunological status among whom 73 (32.7%) started treatment, 15 (6.7%) requested transfer to another health facility, 105 (47.1%) and 30 (13.5%) were lost to follow-up and died respectively without starting ART. The median survival following eligibility for children who died without starting treatment was 2.8?months (IQR: 0.9 - 5.8) with over half (60%) of all deaths occurring at home. ART-eligible children less than 2?years of age and those in WHO stage 3 or 4 were significantly more likely to be LTFU when compared with their respective comparison groups. The overall pre-treatment mortality rate was 25.7 per 100 child-years of follow-up (95% CI 19.9 - 36.8) and the loss to programme rate was 115.7 per 100 child-years of follow-up (95% CI 98.8 - 137). In the multivariable Cox proportional hazard model, significant independent predictors of loss to programme were being less than 2?years of age and WHO stage 3 or 4. The Adjusted Hazard Ratio (AHR) for loss to programme was 2.06 (95% CI 1.12 ?C 3.83) for being aged less than 2?years relative to being 5?years of age or older and 1.92 (95% CI 1.05 - 3.53) for being in WHO stage 3 or 4 relative to WHO stage 1 or 2.

Conclusions

Earlier enrolment into HIV care is key to achieving better outcomes for HIV infected children in developing countries. Developing strategies to ensure early diagnosis, elimination of obstacles to prompt initiation of therapy and instituting measures to reduce losses to follow-up, will improve the overall outcomes of HIV-infected children.     

A single bout of breast milk expression does not increase resting metabolic rate

Introduction

Breastfeeding women have elevated resting metabolic rate (RMR); however, whether a single bout of lactation increases RMR is unknown. This study aimed to determine if a single bout of lactation acutely increased RMR.

Methods

Twenty-two lactating women (age: 31 ± 0.9 year, body mass index: 27.3 ± 1.2 kg/m²) were recruited. RMR was assessed at baseline and at 1- and 2-h following breast milk expression.

Results

RMR was unchanged in lactating women following a single bout of lactation (baseline: 1437 ± 39; 1 h: 1425 ± 37 2 h: 1440 ± 31 kcal/day) (p > .05). RMR was not correlated to daily milk produced (r = 0.05, p > .05), but was correlated to body mass (r = 0.74, p < .001), fat-free mass (kg) (r = 0.61, p < .01), and fat mass (kg) (r = 0.71, p < .01).

Conclusion

RMR in lactating women appears to be more related to body mass or composition in the postpartum period rather than lactation.     

Comparison of wrist-worn and hip-worn activity monitors under free living conditions

Purpose: Current recommendations state that individuals engage in 150?min of moderate or 75?min of vigorous intensity physical activity (PA) each week. Commercial PA monitors are becoming popular for everyday use. The accuracy of these devices, however, is not well understood. We sought to examine the accuracy of two commercial devices, one wrist and one hip-worn, under free-living conditions.

Methods: Twenty-two subjects wore two commercially available devices and one ActiGraph (AG) for seven consecutive days under normal activity.

Results: Mean steps per day between all three devices differed significantly. No differences were found in moderate-to-vigorous intensity physical activity (MPVA). Daily energy expenditure (EE) also differed significantly between the AG and the commercial devices. Bland–Altman analysis found poor agreement between the AG and the commercial devices with regards to steps and EE, but good agreement in MVPA.

Conclusion: Results suggest that the commercial devices are less accurate in estimating steps and EE. These devices did show good agreement with regards to MVPA, suggesting that they may provide useful feedback for individuals seeking to achieve the current PA guidelines for MVPA. Improvements are needed with regards to steps and EE estimation.