Severe vitamin D deficiency in 6 Canadian First Nation formula-fed infants

Background. Rickets was first described in the 17th century and vitamin D deficiency was recognized as the underlying cause in the early 1900s. Despite this long history, vitamin D deficiency remains a significant health concern. Currently, vitamin D supplementation is recommended in Canada for breast fed infants. There are no recommendations for supplementation in formula-fed infants. Objective. The objective of this report is to bring attention to the risk of severe vitamin D deficiency in high risk, formula fed infants. Design. A retrospective chart review was used to create this clinical case series. Results. Severe vitamin D deficiency was diagnosed in six formula-fed infants over a two-and-a-half year period. All six infants presented with seizures and they resided in First Nation communities located at latitude 54 in the province of Manitoba. While these infants had several risk factors for vitamin D deficiency, they were all receiving cow's milk based formula supplemented with 400 IU/L of vitamin D. Conclusion. This report suggests that current practice with regards to vitamin D supplementation may be inadequate, especially for high-risk infants. Health care professionals providing service to infants in a similar situation should be aware of this preventable condition. Hopefully this would contribute to its prevention, diagnosis and management

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

A mixed methods study to evaluate the feasibility of using the Adolescent Diabetes Needs Assessment Tool App in paediatric diabetes care in preparation for a longitudinal cohort study

An evaluation study was carried out to determine the feasibility of integrating the Adolescent Diabetes Needs Assessment Tool (ADNAT) App into UK paediatric diabetes care, to ascertain best practice standards and to determine methodological recommendations for a future cohort study. Methods A non-randomised, cohort, mixed methods study design was used to ensure equality of access to ADNAT for all participants at three sites in the North West of England. Following UK Medical Research Council guidance, the RE-AIM (reach, effectiveness (potential and perceived), adoption, implementation, maintenance) framework was used to guide study objectives and feasibility outcomes. Patients who completed ADNAT (completers) were compared with those who failed to complete (non-completers). Patients’ glycaemic control (HbA1c) was accessed from their clinical data at baseline and at 6 months, alongside their ADNAT scores which were correlated with changes in HbA1c levels. The diabetes teams (respondents) completed a web-based survey and attended focus group interviews. Results Eighty-nine patients were recruited. Withdrawal rates were low at 4.5% (n = 4). Forty-four patients (49.4%) completed ADNAT, leaving 45 (50.6%) non-completers. There were large baseline differences in HbA1c and variable rates of change at 6 months. After adjusting for baseline HbA1C and site in an analysis of covariance, completers had a lower post-ADNAT mean HbA1C level than non-completers at 6 months (-5.42 mmol/mol, 95% CI −11.48, 0.64). Patients’ glycaemic control (HbA1c) at 6 months correlated reasonably well with their ADNAT scores (Spearman’s rho = 0.46). Survey and focus group data showed that ADNAT was judged to be an effective clinical tool by the diabetes teams. Value to patients was perceived by the teams to be linked to parental support, age and previous diabetes education. The combined data triangulated. It served to capture different dimensions which were used to define changes to achieve practice standards and methodological recommendations. Conclusions The combined data showed that ADNAT has the potential to be a clinically viable tool. It has demonstrated the need for a randomised design that is tailored for a ‘hard to reach’ adolescent population. A cluster randomised controlled trial that involves sequential but random rollout of ADNAT over multiple time periods may be the most appropriate and is currently being considered for the larger study

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

Caspase Dependent Programmed Cell Death in Developing Embryos: A Potential Target for Therapeutic Intervention against Pathogenic Nematodes

Pathogenic nematodes currently infect billions of people around the world and pose serious challenges to the economic welfare and public health in most developing countries. At present, limitations of existing therapies warrant identification of new anti-parasitic drugs/drug targets to effectively treat and control neglected tropical diseases [NTD] caused by nematode pathogens. The current gold standard for measuring/screening drug effectiveness against most helminth parasites is in-vitro assessment of motility of parasites/larvae and larval development assays which fails to provide any conclusive idea about the precise mechanism of death of parasitic worms or their larval stages. Given the huge load of parasites or their larval stages in an infected host, a compound which shows promise in in-vitro/motility screening assays but induces necrotic death in parasites/larvae will be of limited use, as it may elicit severe inflammatory response in infected hosts. In this context, the present study, which demonstrates induction of apoptotic death in developing embryos of a pathogenic nematode as a potential drug target for the first time, and provides scope for high throughput screening of pharmacological agents for their apoptogenicity against nematode embryos, is a step forward to develop novel anti-parasitic measures to challenge NTD caused by nematode pathogens

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Contributions of Mamu-A*01 Status and TRIM5 Allele Expression, But Not CCL3L Copy Number Variation, to the Control of SIVmac251 Replication in Indian-Origin Rhesus Monkeys

CCL3 is a ligand for the HIV-1 co-receptor CCR5. There have recently been conflicting reports in the literature concerning whether CCL3-like gene (CCL3L) copy number variation (CNV) is associated with resistance to HIV-1 acquisition and with both viral load and disease progression following infection with HIV-1. An association has also been reported between CCL3L CNV and clinical sequelae of the simian immunodeficiency virus (SIV) infection in vivo in rhesus monkeys. The present study was initiated to explore the possibility of an association of CCL3L CNV with the control of virus replication and AIDS progression in a carefully defined cohort of SIVmac251-infected, Indian-origin rhesus monkeys. Although we demonstrated extensive variation in copy number of CCL3L in this cohort of monkeys, CCL3L CNV was not significantly associated with either peak or set-point plasma SIV RNA levels in these monkeys when MHC class I allele Mamu-A*01 was included in the models or progression to AIDS in these monkeys. With 66 monkeys in the study, there was adequate power for these tests if the correlation of CCL3L and either peak or set-point plasma SIV RNA levels was 0.34 or 0.36, respectively. These findings call into question the premise that CCL3L CNV is important in HIV/SIV pathogenesis