Factors affecting the levels of protection transferred from mother to offspring following immune challenge.

INTRODUCTION: The transfer of antibodies from mother to offspring is key to protecting young animals from disease and can have a major impact on responses to infection and offspring fitness. Such maternal effects also allow young that may be exposed to disease in early life to focus resources on growth and development at this critical period of development. Maternally transferred antibodies are therefore an important source of phenotypic variation in host phenotype as well as influencing host susceptibility and tolerance to infection across generations. It has previously been assumed the transfer of antibodies is passive and invariant and reflects the level of circulating antibody in the mother at the time of transfer. However, whether females may vary in the relative amount of protection transferred to offspring has seldom been explored. RESULTS: Here we show that females differ widely in the relative amount of specific blood antibodies they transfer to the embryonic environment (range 9.2%-38.4% of their own circulating levels) in Chinese painted quail (Coturnix chinensis). Relative transfer levels were unrelated to the size of a female's own immune response. Furthermore, individual females were consistent in their transfer level, both across different stages of their immune response and when challenged with different vaccine types. The amount of antibody transferred was related to female condition, but baseline antibody responses of mothers were not. However, we found no evidence for any trade-offs between the relative amount of antibody transferred with other measures of reproductive investment. CONCLUSIONS: These results suggest that the relative amount of antibodies transferred to offspring can vary significantly and consistently between females. Levels of transfer may therefore be a separate trait open to manipulation or selection with potential consequences for offspring health and fitness in both wild and domesticated populations

Late-onset fibrodysplasia ossificans progressiva with atypical presentation: A case report

Fribrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by progressive heterotopic ossification of connective tissues, episodic flare-ups and bilateral deformities of the great toe (hallux valgus). As faulty tissue repair processes progressively calcify tissue, patients suffer from swelling and limited mobility in that area. We present a case of a 66-year-old woman who had initially presented at age 54 without the hallux valgus deformity or classic-type flare-ups. As there is currently no cure for FOP, management is mainly symptom control. Physicians should still consider FOP if imaging indicates progressive heterotopic ossification in the absence of hallux valgus in an older patient

Home-based Reach-to-Grasp training for people after stroke is feasible: A pilot randomised controlled trial

© The Author(s) 2016. Objective: To determine feasibility of a randomised controlled trial (RCT) of home-based Reach-to-Grasp training after stroke. Design: single-blind parallel group RCT. Participants: Residual arm deficit less than 12 months post-stroke. Interventions: Reach-to-Grasp training in 14 one-hour therapist's visits over 6 weeks, plus one hour self-practice per day (total 56 hours). Control: Usual care. Main Measures: Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), pre-randomisation, 7, 12, 24 weeks post-randomisation. Results: Forty-seven participants (Reach-to-Grasp=24, usual care=23) were randomised over 17 months. Reach-to-Grasp participants received a median (IQR) 14 (13,14) visits, and performed 157 (96,211) repetitions per visit; plus 30 minutes (22,45) self-practice per day. Usual care participants received 10.5 (5,14) therapist visits, comprising 38.6 (30,45) minutes of arm therapy with 16 (6,24) repetitions of functional tasks per visit. Median ARAT scores in the reach-to-grasp group were 8.5 (3.0,24.0) at baseline and 14.5 (3.5,26.0) at 24 weeks compared to median of 4 at both time points (IQR: baseline (3.0,14.0), 24 weeks (3.0,30.0)) in the usual-care group. Median WMFT tasks completed at baseline and 24 weeks were 6 (3.0,11.5) and 8.5 (4.5,13.5) respectively in the reach-to-grasp group and 4 (3.0,10.0), 6 (3.0,14.0) in the usual care group. Incidence of arm pain was similar between groups. The study was stopped before 11 patients reached the 24 weeks assessment. Conclusions: An RCT of home-based Reach-to-Grasp training after stroke is feasible and safe. With ARAT being our preferred measure it is estimated that 240 participants will be needed for a future two armed trial

Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.

Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data

Identification of Australian Aboriginal and Torres Strait Islander Cancer Patients in the Primary Health Care Setting.

BACKGROUND: Aboriginal and Torres Strait Islander Australians have poorer cancer outcomes and experience 30% higher mortality rates compared to non-Indigenous Australians. Primary health care (PHC) services are increasingly being recognized as pivotal in improving Indigenous cancer patient outcomes. It is currently unknown whether patient information systems and practices in PHC settings accurately record Indigenous and cancer status. Being able to identify Indigenous cancer patients accessing services in PHC settings is the first step in improving outcomes. METHODS: Aboriginal Medical Centres, mainstream (non-Indigenous specific), and government-operated centers in Queensland were contacted and data were collected by telephone during the period from 2014 to 2016. Participants were asked to (i) identify the number of patients diagnosed with cancer attending the service in the previous year; (ii) identify the Indigenous status of these patients and if this information was available; and (iii) advise how this information was obtained. RESULTS: Ten primary health care centers (PHCCs) across Queensland participated in this study. Four centers were located in regional areas, three in remote areas and three in major cities. All participating centers reported ability to identify Indigenous cancer patients attending their service and utilizing electronic Patient Care Information Systems (PCIS) to manage their records; however, not all centers were able to identify Indigenous cancer patients in this way. Indigenous cancer patients were identified by PHCCs using PCIS (n = 8), searching paper records (n = 1), and combination of PCIS and staff recall (n = 1). Six different types of PCIS were being utilized by participating centers. There was no standardized way to identify Indigenous cancer patients across centers. Health service information systems, search functions and capacities of systems, and staff skill in extracting data using PCIS varied between centers. CONCLUSION: It is crucial to be able to easily identify Indigenous cancer patients accessing health services in the PHC setting to monitor progress, improve and evaluate care, and ultimately improve Indigenous cancer outcomes. It is also important for PHC staff to receive adequate training and support to utilize PCISs efficiently and effectively

Correlated physical and mental health summary scores for the SF-36 and SF-12 Health Survey, V.1

<p>Abstract</p> <p>Background</p> <p>The SF-36 and SF-12 summary scores were derived using an uncorrelated (orthogonal) factor solution. We estimate SF-36 and SF-12 summary scores using a correlated (oblique) physical and mental health factor model.</p> <p>Methods</p> <p>We administered the SF-36 to 7,093 patients who received medical care from an independent association of 48 physician groups in the western United States. Correlated physical health (PCS_c) and mental health (MCS_c) scores were constructed by multiplying each SF-36 scale z-score by its respective scoring coefficient from the obliquely rotated two factor solution. PCS_c-12 and MCS_c-12 scores were estimated using an approach similar to the one used to derive the original SF-12 summary scores.</p> <p>Results</p> <p>The estimated correlation between SF-36 PCS_cand MCS_cscores was 0.62. There were far fewer negative factor scoring coefficients for the oblique factor solution compared to the factor scoring coefficients produced by the standard orthogonal factor solution. Similar results were found for PCS_c-12, and MCS_c-12 summary scores.</p> <p>Conclusion</p> <p>Correlated physical and mental health summary scores for the SF-36 and SF-12 derived from an obliquely rotated factor solution should be used along with the uncorrelated summary scores. The new scoring algorithm can reduce inconsistent results between the SF-36 scale scores and physical and mental health summary scores reported in some prior studies.</p> <p>(Subscripts C = correlated and UC = uncorrelated)</p

Hip fracture risk assessment: Artificial neural network outperforms conditional logistic regression in an age- and sex-matched case control study

Copyright @ 2013 Tseng et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background - Osteoporotic hip fractures with a significant morbidity and excess mortality among the elderly have imposed huge health and economic burdens on societies worldwide. In this age- and sex-matched case control study, we examined the risk factors of hip fractures and assessed the fracture risk by conditional logistic regression (CLR) and ensemble artificial neural network (ANN). The performances of these two classifiers were compared. Methods - The study population consisted of 217 pairs (149 women and 68 men) of fractures and controls with an age older than 60 years. All the participants were interviewed with the same standardized questionnaire including questions on 66 risk factors in 12 categories. Univariate CLR analysis was initially conducted to examine the unadjusted odds ratio of all potential risk factors. The significant risk factors were then tested by multivariate analyses. For fracture risk assessment, the participants were randomly divided into modeling and testing datasets for 10-fold cross validation analyses. The predicting models built by CLR and ANN in modeling datasets were applied to testing datasets for generalization study. The performances, including discrimination and calibration, were compared with non-parametric Wilcoxon tests. Results - In univariate CLR analyses, 16 variables achieved significant level, and six of them remained significant in multivariate analyses, including low T score, low BMI, low MMSE score, milk intake, walking difficulty, and significant fall at home. For discrimination, ANN outperformed CLR in both 16- and 6-variable analyses in modeling and testing datasets (p?<?0.005). For calibration, ANN outperformed CLR only in 16-variable analyses in modeling and testing datasets (p?=?0.013 and 0.047, respectively). Conclusions - The risk factors of hip fracture are more personal than environmental. With adequate model construction, ANN may outperform CLR in both discrimination and calibration. ANN seems to have not been developed to its full potential and efforts should be made to improve its performance.National Health Research Institutes in Taiwa

Environmental and Parental Influences on Offspring Health and Growth in Great Tits (Parus major)

PMCID: PMC3728352This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The future of canine glaucoma therapy

Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irreversible vision loss in dogs and may be either primary or secondary. Despite the growing spectrum of medical and surgical therapies, there is no cure, and many affected dogs go blind. Often eyes are enucleated because of painfully high, uncontrollable IOP. While progressive vision loss due to primary glaucoma is considered preventable in some humans, this is mostly not true for dogs. There is an urgent need for more effective, affordable treatment options. Because newly developed glaucoma medications are emerging at a very slow rate and may not be effective in dogs, work toward improving surgical options may be the most rewarding approach in the near term. This Viewpoint Article summarizes the discussions and recommended research strategies of both a Think Tank and a Consortium focused on the development of more effective therapies for canine glaucoma; both were organized and funded by the American College of Veterinary Ophthalmologists Vision for Animals Foundation (ACVO‐VAF). The recommendations consist of (a) better understanding of disease mechanisms, (b) early glaucoma diagnosis and disease staging, (c) optimization of IOP‐lowering medical treatment, (d) new surgical therapies to control IOP, and (e) novel treatment strategies, such as gene and stem cell therapies, neuroprotection, and neuroregeneration. In order to address these needs, increases in research funding specifically focused on canine glaucoma are necessary.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151896/1/vop12678_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151896/2/vop12678.pd

Surveying uveitis specialists—a call for consensus

Thomas Brennan became disillusioned with popular law school rankings and so decided to survey 100 academics, judges, and lawyers on his own, asking them to rank a list of ten schools he provided. He used a composite index similar in structure, but different in content, to those used by main-stream surveyors, such as U.S. News &amp; World Report. As expected, many of the big name schools—Harvard, Yale, Stanford—made it to the top of the list. Penn State, as Brennan recalled, “[Was] about in the middle of the pack. Maybe fifth among the 10 schools listed. ” There was one small problem, however. Penn State had no law school at the time. Brennan had included it to make a point: surveys are limited by both the quality of the questions asked and by how familiar respondents are with the subject being surveyed [1, 2]