Does the risk of cerebral palsy increase or decrease with increasing gestational age?

BACKGROUND: It is generally accepted that the risk of cerebral palsy decreases with increasing gestational age of live born infants. However, recent studies have shown that cerebral palsy often has prenatal antecedents including congenital malformations, vascular insults and maternal infection. Cerebral palsy is therefore better viewed as occurring among fetuses, rather than among infants. We explored the epidemiologic implications of this change in perspective. METHODS: We used recently published data from Shiga Prefecture, Japan and from North-East England to examine the pattern of gestational age-specific rates of cerebral palsy under these alternative perspectives. We first calculated gestational age-specific rates of cerebral palsy as per convention, by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of live births in that gestational age category. Under the alternative formulation, we calculated gestational age-specific rates of cerebral palsy by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of fetuses who were at risk of being born at that gestation and being afflicted with cerebral palsy. RESULTS: Under the conventional formulation, cerebral palsy rates decreased with increasing gestational age from 63.9 per 1,000 live births at <28 weeks gestation to 0.9 per 1,000 live births at 37 or more weeks gestation. When fetuses were viewed as potential candidates for cerebral palsy, cerebral palsy rates increased with increasing gestational age from 0.08 per 1,000 fetuses at risk at <28 weeks gestation to 0.9 per 1,000 fetuses at risk at 37 or more weeks gestation. CONCLUSIONS: The fetuses-at-risk approach is the appropriate epidemiologic formulation for calculating the gestational age-specific rate of cerebral palsy from a causal perspective. It shows that the risk of cerebral palsy increases as gestational duration increases. This compelling view of cerebral palsy risk may help refocus research aimed at understanding and preventing cerebral palsy

The impact of decision aids to enhance shared decision making for diabetes (the DAD study): protocol of a cluster randomized trial

Background. Shared decision making contributes to high quality healthcare by promoting a patientcentered approach. Patient involvement in selecting the components of a diabetes medication program that best match the patient's values and preferences may also enhance medication adherence and improve outcomes. Decision aids are tools designed to involve patients in shared decision making, but their adoption in practice has been limited. In this study, we propose to obtain a preliminary estimate of the impact of patient decision aids vs. usual care on measures of patient involvement in decision making, diabetes care processes, medication adherence, glycemic and cardiovascular risk factor control, and resource utilization. In addition, we propose to identify, describe, and explain factors that promote or inhibit the routine embedding of decision aids in practice. Methods. We will be conducting a mixed-methods study comprised of a cluster-randomized, practical, multicentered trial enrolling clinicians and their patients (n = 240) with type 2 diabetes from rural and suburban primary care practices (n = 8), with an embedded qualitative study to examine factors that influence the incorporation of decision aids into routine practice. The intervention will consist of the use of a decision aid (Statin Choice and Aspirin Choice, or Diabetes Medication Choice) during the clinical encounter. The qualitative study will include analysis of video recordings of clinical encounters and in-depth, semi-structured interviews with participating patients, clinicians, and clinic support staff, in both trial arms. Discussion. Upon completion of this trial, we will have new knowledge about the effectiveness of diabetes decision aids in these practices. We will also better understand the factors that promote or inhibit the successful implementation and normalization of medication choice decision aids in the care of chronic patients in primary care practices

Identifying Molecular Effects of Diet through Systems Biology: Influence of Herring Diet on Sterol Metabolism and Protein Turnover in Mice

BACKGROUND: Changes in lifestyle have resulted in an epidemic development of obesity-related diseases that challenge the healthcare systems worldwide. To develop strategies to tackle this problem the focus is on diet to prevent the development of obesity-associated diseases such as cardiovascular disease (CVD). This will require methods for linking nutrient intake with specific metabolic processes in different tissues. METHODOLOGY/PRINCIPAL FINDING: Low-density lipoprotein receptor-deficient (Ldlr -/-) mice were fed a high fat/high sugar diet to mimic a westernized diet, being a major reason for development of obesity and atherosclerosis. The diets were supplemented with either beef or herring, and matched in macronutrient contents. Body composition, plasma lipids and aortic lesion areas were measured. Transcriptomes of metabolically important tissues, e.g. liver, muscle and adipose tissue were analyzed by an integrated approach with metabolic networks to directly map the metabolic effects of diet in these different tissues. Our analysis revealed a reduction in sterol metabolism and protein turnover at the transcriptional level in herring-fed mice. CONCLUSION: This study shows that an integrated analysis of transcriptome data using metabolic networks resulted in the identification of signature pathways. This could not have been achieved using standard clustering methods. In particular, this systems biology analysis could enrich the information content of biomedical or nutritional data where subtle changes in several tissues together affects body metabolism or disease progression. This could be applied to improve diets for subjects exposed to health risks associated with obesity

Single origin of sex chromosomes and multiple origins of B chromosomes in fish genus Characidium

Chromosome painting with DNA probes obtained from supernumerary (B) and sex chromosomes in three species of fish genus Characidium (C. gomesi, C. pterostictum and C. oiticicai) showed a close resemblance in repetitive DNA content between B and sex chromosomes in C. gomesi and C. pterostictum. This suggests an intraspecific origin for B chromosomes in these two species, probably deriving from sex chromosomes. In C. oiticicai, however, a DNA probe obtained from its B chromosome hybridized with the B but not with the A chromosomes, suggesting that the B chromosome in this species could have arisen interspecifically, although this hypothesis needs further investigation. A molecular phylogenetic analysis performed on nine Characidium species, with two mtDNA genes, showed that the presence of heteromorphic sex chromosomes in these species is a derived condition, and that their origin could have been unique, a conclusion also supported by interspecific chromosome painting with a CgW probe derived from the W chromosome in C. gomesi. Summing up, our results indicate that whereas heteromorphic sex chromosomes in the genus Characidium appear to have had a common and unique origin, B chromosomes may have had independent origins in different species. Our results also show that molecular phylogenetic analysis is an excellent complement for cytogenetic studies by unveiling the direction of evolutionary chromosome changes.This research was funded by grants from the State of Sao Paulo Research Foundation (FAPESP) to EAS (2013/02143-3), grants from National Council for Research and Development (CNPq) to FF (480449/2012-0), and by Coordenacao de Aperfeicoamento de Pessoal de Nıvel Superior (CAPES)

Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE'): study protocol

<p>Abstract</p> <p>Background</p> <p>Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction.</p> <p>Methods/Design</p> <p>Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m²) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin.</p> <p>Discussion</p> <p>While clinical data indicate that excess weight for height is associated with poor prognosis for long term survival, little attention is paid to weight control in the clinical management of breast cancer. This study will provide information that can be used to answer important patient questions about the effects of dietary pattern and magnitude of weight loss on long term survival following breast cancer treatment.</p> <p>Clinical Trial Registration</p> <p>CA125243</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Physical evidence for the induced release of the Bacillus subtilis transcription factor, sigma(F), from its inhibitory complex.

The release of the transcription factor sigma(F) from its inhibitory complex with SpoIIAB is a key regulatory step in the control of sporulation in Bacillus subtilis as it initiates a pattern of differential gene expression in the mother cell and prespore compartments. The sigma(F).SpoIIAB complex is dissociated by the unphosphorylated form of the protein SpoIIAA, the alternative binding partner of SpoIIAB. Here, we employ fluorescence spectroscopy to examine the mechanism by which SpoIIAA acts on the sigma(F).SpoIIAB complex. We constructed a mutant of sigma(F), sigma(F)-W46L, which displayed a reproducible fluorescence response on binding to SpoIIAB. Using this mutant we were able to quantify the amount of sigma(F) bound to SpoIIAB in real time. The results provide physical evidence for the "induced release" mechanism of sigma(F) activation. We demonstrate that SpoIIAA interacts directly with the sigma(F).SpoIIAB complex, greatly decreasing the affinity of SpoIIAB for sigma(F) and thus causing the release of the latter. We also demonstrate that sigma(F) is released before SpoIIAA is phosphorylated and that release occurs on a similar time scale to the binding of SpoIIAA to SpoIIAB