Background We previously reported in a cross-sectional study that patients who were in periodontal maintenance programs and were taking vitamin D and calcium supplementation had a trend for better periodontal health compared with patients not taking supplementation. The objective of the present study was to determine, for the same group of subjects, whether there was a difference in periodontal health over a one–year period. Methods Fifty-one patients enrolled in maintenance programs from two dental clinics were recruited. Twenty-three were taking vitamin D (≥400 international units/day) and calcium (≥1000mg/day) supplementation, and twenty-eight were not taking supplementation. All subjects had ≥2 interproximal sites with ≥3 mm clinical attachment loss. For mandibular-posterior teeth, these clinical parameters were recorded: gingival index, plaque index, probing depth, attachment loss, bleeding upon probing, calculus index and furcation involvement. Photostimulable-phosphor, posterior bitewing radiographs were taken to assess alveolar bone. Daily vitamin D and calcium intakes were estimated by nutritional analysis. Data were collected at baseline, 6 months, and 12 months. Results Clinical parameters improved with time in both groups (p<0.01). When clinical measures were considered collectively, the results were borderline significant at baseline (p=0.061), significant at 6 months (p=0.049) but not significant at 12 months (p=0.114). After adjusting for covariates, the effect of supplements was significant at baseline (p=0.037), borderline at 6 months (p=0.058) and not significant at 12 months (p=0.142) Conclusion Calcium and vitamin D supplementation has a modest positive effect on periodontal health, and consistent dental care improves clinical parameters of periodontal disease regardless of such supplements. Calcium and vitamin D supplementation has a modest positive effect on periodontal health, and consistent dental care improves clinical parameters of periodontal disease regardless of such supplements. Our findings raise the possibility that vitamin D, perhaps at higher doses, may positively impact on periodontal disease severity.

Background Low dietary intakes of vitamin D and calcium hasten bone loss and osteoporosis. Because vitamin D metabolites may also alter the inflammatory response and have anti-microbial effects, we studied whether use of vitamin D and calcium supplements affects periodontal disease status. Methods A cohort of 51 subjects receiving periodontal maintenance therapy was recruited from 2 dental clinics. Of these, 23 were taking vitamin D (≥400 international units/day) and calcium (≥1000mg/day) supplementation, and 28 were not taking such supplementation. All subjects had ≥2 interproximal sites with ≥3 mm clinical attachment loss. Daily calcium and vitamin D intakes (from food and supplements) were estimated by nutritional analysis. The following clinical parameters of periodontal disease were recorded for the mandibular posterior teeth: gingival index, probing depth, cementoenamel junction-gingival margin distance (attachment loss), bleeding upon probing, and furcation involvement. Posterior photostimulable-phosphor bitewing radiographs were taken to determine cementoenamel-junction-alveolar-crest distances (alveolar crest height loss). Data were analyzed with a repeated-measures, multivariate analysis of variance. Results Relative to subjects who did not take vitamin D and calcium supplementation, supplement takers had shallower probing depths, fewer bleeding sites, lower gingival index values, fewer furcation involvements, less attachment loss and less alveolar crest height loss. The repeated-measures analysis indicated that collectively these differences for clinical parameters were borderline significant (P=0.08). Conclusion In these subjects receiving periodontal maintenance therapy, there was a trend for better periodontal health with intake of vitamin D and calcium supplementation. More expanded longitudinal studies are required to determine the potential of this relationship.

A critical window (sensitive period) represents a period during development when an organism's phenotype is responsive to intrinsic or extrinsic (environmental) factors. Such windows represent a form of developmental phenotypic plasticity and result from the interaction between genotype and environment. Critical windows have typically been defined as comprising discrete periods in development with a distinct starting time and end time, as identified by experiments following an on and an off protocol. Yet in reality, periods of responsiveness during development are likely more ambiguous that depicted. Our goal is to extend the concept of the developmental critical window by introducing a three-dimensional construct in which time during development, dose of the stressor applied, and the resultant phenotypic modification can be utilized to more realistically define a critical window. Using the example of survival of the brine shrimp (Artemia franciscana) during exposure to different salinity levels during development, we illustrate that it is not just stressor dose or exposure time but the interaction of these two factors that results in the measured phenotypic change, which itself may vary within a critical window. We additionally discuss a systems approach to critical windows, in which the components of a developing system--whether they be molecular, physiological, or morphological--may show differing responses with respect to time and dose. Thus, the plasticity of each component may contribute to a broader overall system response.

The timing, success and energetics of fish embryonic development are strongly influenced by temperature. However, it is unclear if there are developmental periods, or critical windows, when oxygen use, survival and hatchling phenotypic characteristics are particularly influenced by changes in the thermal environment. Therefore, we examined the effects of constant incubation temperature and thermal shifts on survival, hatchling phenotype, and cost of development in lake whitefish (Coregonus clupeaformis) embryos. We incubated whitefish embryos at control temperatures of 2, 5, or 8 °C, and shifted embryos across these three temperatures at the end of gastrulation or organogenesis. We assessed hatch timing, mass at hatch, and yolk conversion efficiency (YCE). We determined cost of development, the amount of oxygen required to build a unit of mass, for the periods from fertilization-organogenesis, organogenesis-fin flutter, fin flutter-hatch, and for total development. An increase in incubation temperature decreased time to 50 % hatch (164 days at 2 °C, 104 days at 5 °C, and 63 days at 8 °C), survival decreased from 55 % at 2 °C, to 38 % at 5 °C, and 17 % at 8 °C, and hatchling yolk-free dry mass decreased from 1.27 mg at 2 °C to 0.61 mg at 8 °C. Thermal shifts altered time to 50 % hatch and hatchling yolk-free dry mass and revealed a critical window during gastrulation in which a temperature change reduced survival. YCE decreased and cost of development increased with increased incubation temperature, but embryos that hatched at 8 °C and were incubated at colder temperatures during fertilization-organogenesis had reduced cost. The relationship between cost of development and temperature was altered during fin flutter-hatch, indicating it may be a critical window during which temperature has the greatest impact on energetic processes. The increase in cost of development with an increase in temperature has not been documented in other fishes and suggests whitefish embryos are more energy efficient at colder temperatures.

Critical oxygen pressure (P(C)) is used in respiratory physiology to measure the response to hypoxia. P(C) defines the partial pressure of oxygen (Po(2)) at which an oxygen regulator switches to a conformer. However, not all animals show such clear patterns in oxygen consumption rate (Mo2), and there are many methods for determining P(C). This study assesses two methods that determine regulatory ability and four that calculate P(C). A new method, the regulation index (RI), assigns to an animal a relative measure of regulatory ability by calculating the area under the Mo2 versus Po(2) curve that is greater than a linear trend. The six methods are applied to developmental Mo2 data of two amphibians, Pseudophryne bibronii and Crinia georgiana. The four methods used to determine P(C) produced similar results but failed to identify the increase in regulation on hatching in C. georgiana or the greater regulation in larval C. georgiana compared with P. bibronii. Of the two methods that evaluated regulation, only the RI satisfactorily represented the entire range of Po(2). The RI is advantageous because it has clearly defined limits and does not constrain data to fit any single pattern. The RI can be used in concert with P(C), which can be easily calculated during the RI analysis, to provide a clearer definition of the Mo2 response to environmental Po(2).

Purpose Polymorphisms in the CYP19A1 (aromatase) gene have been reported to influence disease-free survival and the incidence of musculoskeletal complaints in patients taking aromatase inhibitors (AIs) for estrogen receptor positive (ER+) breast cancer. Bone loss and fractures are wellrecognized complications from AI therapy. The objective of this study is to determine the influence of polymorphisms in the CYP19A1 gene on bone loss among patients taking aromatase inhibitors for ER+ breast cancer. Patients and Methods The subjects consisted of 97 postmenopausal women with ER+ breast cancer who were initiated on third-generation AIs. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry at baseline and at 6 and 12 months. Twenty-four hour urine N-telopeptide (NTX) was measured by Elisa and serum estradiol was measured by ultrasensitive radioimmunoassay at baseline, and at 6 months. Genotyping was done by Taqman SNP allelic discrimination assay. Results Women with the AA genotype for the rs700518 (G/A at Val80) developed significant bone loss at the lumbar spine and the total hip at 12 months relative to patients carrying the G allele (GA/GG); both p=0.03. There was a borderline greater increase in urinary NTX in those with the AA genotype compared to patients with the G allele, p=0.05; but no significant difference in changes in estradiol levels among the genotypes. Conclusion Patients with the AA genotype for the rs700518 polymorphism in the CYP19A1 gene are at risk for AI-associated bone loss and deserve close follow-up during long-term AI therapy.

The inaugural Kjell Johansen Lecture in the Zoophysiology Department of Aarhus University (Aarhus, Denmark) afforded the opportunity for a focused workshop comprising comparative cardiovascular physiologists to ponder some of the key unanswered questions in the field. Discussions were centred around three themes. The first considered function of the vertebrate heart in its various forms in extant vertebrates, with particular focus on the role of intracardiac shunts, the trabecular ('spongy') nature of the ventricle in many vertebrates, coronary blood supply and the building plan of the heart as revealed by molecular approaches. The second theme involved the key unanswered questions in the control of the cardiovascular system, emphasizing autonomic control, hypoxic vasoconstriction and developmental plasticity in cardiovascular control. The final theme involved poorly understood aspects of the interaction of the cardiovascular system with the lymphatic, renal and digestive systems. Having posed key questions around these three themes, it is increasingly clear that an abundance of new analytical tools and approaches will allow us to learn much about vertebrate cardiovascular systems in the coming years.

This review explores challenges and opportunities in developmental physiology outlined by a symposium at the 2014 American Physiological Society Intersociety Meeting: Comparative Approaches to Grand Challenges in Physiology. Across animal taxa, adverse embryonic/fetal environmental conditions can alter morphological and physiological phenotypes in juveniles or adults, and capacities for developmental plasticity are common phenomena. Human neonates with body sizes at the extremes of perinatal growth are at an increased risk of adult disease, particularly hypertension and cardiovascular disease. There are many rewarding areas of current and future research in comparative developmental physiology. We present key mechanisms, models, and experimental designs that can be used across taxa to investigate patterns in, and implications of, the development of animal phenotypes. Intraspecific variation in the timing of developmental events can be increased through developmental plasticity (heterokairy), and could provide the raw material for selection to produce heterochrony — an evolutionary change in the timing of developmental events. Epigenetics and critical windows research recognizes that in ovo or fetal development represent a vulnerable period in the life history of an animal, when the developing organism may be unable to actively mitigate environmental perturbations. ‘Critical windows’ are periods of susceptibility or vulnerability to environmental or maternal challenges, periods when recovery from challenge is possible, and periods when the phenotype or epigenome has been altered. Developmental plasticity may allow survival in an altered environment, but it also has possible long-term consequences for the animal. “Catch-up growth” in humans after the critical perinatal window has closed elicits adult obesity and exacerbates a programmed hypertensive phenotype (one of many examples of “fetal programing”). Grand challenges for developmental physiology include integrating variation in developmental timing within and across generations, applying multiple stressor dosages and stressor exposure at different developmental timepoints, assessment of epigenetic and parental influences, developing new animal models and techniques, and assessing and implementing these designs and models in human health and development.