Salivary iodide status as a measure of whole body iodine homoeostasis?

Iodine is a trace element required to produce the thyroid hormones, which are critical for development, growth and metabolism. To ensure appropriate population iodine nutrition, convenient and accurate methods of monitoring are necessary. Current methods for determining iodine status either involve a significant participant burden or are subject to considerable intra-individual variation. The continuous secretion of iodide in saliva potentially permits its use as a convenient, non-invasive assessment of status in populations. To assess its likely effectiveness, we reviewed studies analysing the association between salivary iodide concentration (SIC) and dietary iodine intake, urinary iodide concentration (UIC) and/or 24-h urinary iodide excretion (UIE). Eight studies conducted in different countries met the inclusion criteria, including data for 921 subjects: 702 healthy participants and 219 with health conditions. SIC correlated positively with UIC and/or UIE in four studies, with the strength of relationship ranging from r = 0·19 to r = 0·90 depending on sampling protocol, age, and if salivary values were corrected for protein concentration. Additionally, SIC positively correlated with dietary intake, being strongest when saliva was collected after dinner. SIC varied with external factors, including thyroid function, use of some medications, smoking and overall health status. Evidence provided here supports the use of SIC as a viable, low-burden method for determining iodine status in populations. However, small sample sizes and high variability indicates the need for more extensive analyses across age groups, ethnicities, disease states and dietary groups to clarify the relative accuracy and reliability in each case and standardise procedure.

Systematic review and meta-analysis of iodine nutrition in modern vegan and vegetarian diets.

Vegan and vegetarian diets are widely supported and adopted, but individuals following such diets remain at greater risk of iodine deficiency. This systematic review and meta-analysis was conducted to assess the iodine intake and status in adults following a vegan or vegetarian diet in the modern day. A systematic review and quality assessment were conducted from October 2020 to December 2022 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidance. Studies were identified in Ovid MEDLINE, Web of Science, PubMed, and Scopus. Eleven articles were eligible for review containing 4421 adults (aged ≥ 18 years). Vegan groups had the lowest median urinary iodine concentration (mUIC) (12·2/l). None of the dietary groups had mUIC within the optimal range for iodine status (100-200 µg/l) (WHO). Vegan diets had the poorest iodine intake (17·3 µg/d) and were strongly associated with lower iodine intake (P = < 0·001) compared with omnivorous diets. Lower intake in vegan diets was influenced by sex (P = 0·007), the presence of voluntary or absence of Universal Salt Iodisation (USI) programmes (P = 0·01 & P = < 0·001), and living in a country with adequate iodine nutrition (P = < 0·001). Vegetarians and particularly vegans living in countries with no current USI programme continue to have increased risk of low iodine status, iodine deficiency and inadequate iodine intake. Further research into the usefulness of mandatory fortification of vegan appropriate foods is required.

When less is more: does more Na+-cations mean more adsorption sites for toluene in faujasites?

The unique properties of zeolites make them an interesting material to be used in separation processes. The possibility of tailoring some of their characteristics, like the Si/Al ratio, allows optimizing their synthesis for a given task. Concerning the adsorption of toluene by faujasites an understanding of the effect of cations is necessary to foster the elaboration of new materials, which can capture molecules with a high degree of selectivity and sensitivity. Undoubtedly, this knowledge is relevant for a wide range of applications going from the elaboration of technologies for improving the air-quality to diagnostic procedures to prevent health risks. The studies reported here using Grand Canonical Monte Carlo simulations elucidate the role of Na-cations in the adsorption of toluene by faujasites with different Si/Al ratios. They detail how the location of the cations inhibits or enhances the adsorption. The cations located at site II are shown to be those enhancing the adsorption of toluene on faujasites. Interestingly, the cations located at site III generate a hindrance at high loading. This becomes an impediment for the organization of toluene molecules inside faujasites.

Toward the development of sensors for lung cancer: The adsorption of 1-propanol on hydrophobic zeolites.

A healthy breath is mainly composed of water, carbon dioxide, molecular nitrogen, and oxygen and it contains many species, in small quantities, which are related to the ambient atmosphere and the metabolism. The breath of a person affected by lung cancer presents a concentration of 1-propanol higher than usual. In this context, the development of specific sensors to detect 1-propanol from breath is of high interest. The amount of propanol usually detected on the breath is of few ppb; this small quantity is a handicap for a reliable diagnostic. This limitation can be overcome if the sensor is equipped with a pre-concentrator. Our studies aim to provide an efficient material playing this role. This will contribute to the development of reliable and easy to use lung cancer detectors. For this, we investigate the properties of a few hydrophobic porous materials (chabazite, silicalite-1, and dealuminated faujasite). Hydrophobic structures are used to avoid saturation of materials by the water present in the exhaled breath. Our experimental and simulation results suggest that silicalite -1 (MFI) is the most suitable structure to be used as a pre-concentrator.

Influence of kinematic alignment on femorotibial kinematics in medial stabilized TKA design compared to mechanical alignment.

INTRODUCTION: Worldwide more and more primary knee replacements are being performed. Kinematic alignment (KA) as one of many methods of surgical alignment has been shown to have a significant impact on kinematics and function. The aim of the present study was to compare KA and mechanical alignment (MA) with regard to femorotibial kinematics. MATERIALS AND METHODS: Eight fresh frozen human specimens were tested on a knee rig during active knee flexion from 30 to 130°. Within the same specimen a medial stabilized (MS) implant design was used first with KA and then with MA. RESULTS: The femorotibial kinematics showed more internal rotation of the tibia in KA compared to MA. At the same time, there was a larger medial rotation point in KA. Both alignment methods showed femoral rollback over the knee bend. CONCLUSION: Relating to an increased internal rotation and a more precise medial pivot point, it can be concluded that KA combined with a MS implant design may partially support the reproduction of physiological knee joint mechanics.

Plant community responses to experimental climate manipulation in a Welsh ombrotrophic peatland and their palaeoenvironmental context.

We test whether vegetation community composition from a 10-year climate manipulation experiment on a Welsh peat bog resembles vegetation communities during periods of climate change inferred from a peat core. Experimentally warmed and combined warmed and droughted treatments drove significant increases in ericaceous shrubs but Sphagnum was unaffected. Similarly, Calluna vulgaris seeds increase during inferred warmer periods in the palaeoecological record. Experimental short-term episodic drought (four 4-week drought treatments) did not affect vegetation. Plant community composition has undergone several abrupt changes throughout the past c. 1500 years, often in response to human disturbance. Only slight changes occurred during the Medieval Climate Anomaly (c. 950-1250 Common Era [CE]) in vegetation and hydrology, while abrupt changes occurred during the Little Ice Age (c. 1300-1850 CE) when water tables were highest, suggesting that these shifts were driven by changes in water table, modulated by climate. A period of water table drawdown c. 1800, synchronous with historical records of increased drainage, corresponds with the development of the present-day vegetation community. Modern analogues for fossil material, characterized by abundant Rhynchospora alba and Sphagnum pulchrum, are more common after this event. Vegetation changes due to climate inferred from the palaeo record differ from those observed in the experiments, possibly relating to differences in the importance of drivers of vegetation change over varying timescales. Whereas temperature is frequently identified as the dominant driver of plant community change in experiments, sustained changes in water table appear to be more important in the long-term record. We find evidence that recent climate change and other anthropogenic stressors (e.g. drainage, heavy metal and nitrogen pollution) may promote the development of novel plant communities without analogues in the fossil record. These communities may be poorer at sequestering carbon and may respond differently to future climate change.

Kirkwood-Buff integrals: From fluctuations in finite volumes to the thermodynamic limit.

The Kirkwood-Buff theory is a cornerstone of the statistical mechanics of liquids and solutions. It relates volume integrals over the radial distribution function, so-called Kirkwood-Buff integrals (KBIs), to particle number fluctuations and thereby to various macroscopic thermodynamic quantities such as the isothermal compressibility and partial molar volumes. Recently, the field has seen a strong revival with breakthroughs in the numerical computation of KBIs and applications to complex systems such as bio-molecules. One of the main emergent results is the possibility to use the finite volume KBIs as a tool to access finite volume thermodynamic quantities. The purpose of this Perspective is to shed new light on the latest developments and discuss future avenues.

Neurological side effects of radiation therapy.

Radiation therapy (RT) is one of the main treatments administered to patients with cancer. The development of technology has improved RT accuracy by allowing more precise delivery of high doses to the target volumes with reduced exposure of healthy tissue. Life expectancy has increased due to these therapeutic advancements and the patients' quality of life remains a major concern. The adverse events related to RT are quite various and most likely will impair essential neurological functions, e.g. cognitive status. This literature review aims to describe the physiopathological processes, the neurological symptoms as well as the local modifications observed in magnetic resonance imaging following RT. The specific therapeutic options and preventive actions will also be discussed.

Dosimetry and Calorimetry Performance of a Scientific CMOS Camera for Environmental Monitoring.

This paper explores the prospect of CMOS devices to assay lead in drinking water, using calorimetry. Lead occurs together with traces of radioisotopes, e.g., 210Pb, producing g-emissions with energies ranging from 10 keV to several 100 keV when they decay; this range is detectable in silicon sensors. In this paper we test a CMOS camera (OXFORD INSTRUMENTS Neo 5.5) for its general performance as a detector of X-rays and low energy g-rays and assess its sensitivity relative to the World Health Organization upper limit on lead in drinking water. Energies from 6 keV to 60 keV are examined. The CMOS camera has a linear energy response over this range and its energy resolution is for the most part slightly better than 2%. The Neo sCMOS is not sensitive to X-rays with energies below ~10 keV. The smallest detectable rate is 40 ± 3 mHz, corresponding to an incident activity on the chip of 7 ± 4 Bq. The estimation of the incident activity sensitivity from the detected activity relies on geometric acceptance and the measured efficiency vs. energy. We report the efficiency measurement, which is 0.08(2)% (0.0011(2)%) at 26.3 keV (59.5 keV). Taking calorimetric information into account we measure a minimal detectable rate of 4 ± 1 mHz (1.5 ± 0.1 mHz) for 26.3 keV (59.5 keV) g-rays, which corresponds to an incident activity of 1.0 ± 0.6 Bq (57 ± 33 Bq). Toy Monte Carlo and Geant4 simulations agree with these results. These results show this CMOS sensor is well-suited as a g- and X-ray detector with sensitivity at the few to 100 ppb level for 210Pb in a sample.

Opioid suppression of conditioned anticipatory brain responses to breathlessness.

Opioid painkillers are a promising treatment for chronic breathlessness, but are associated with potentially fatal side effects. In the treatment of breathlessness, their mechanisms of action are unclear. A better understanding might help to identify safer alternatives. Learned associations between previously neutral stimuli (e.g. stairs) and repeated breathlessness induce an anticipatory threat response that may worsen breathlessness, contributing to the downward spiral of decline seen in clinical populations. As opioids are known to influence associative learning, we hypothesized that they may interfere with the brain processes underlying a conditioned anticipatory response to breathlessness in relevant brain areas, including the amygdala and the hippocampus. Healthy volunteers viewed visual cues (neutral stimuli) immediately before induction of experimental breathlessness with inspiratory resistive loading. Thus, an association was formed between the cue and breathlessness. Subsequently, this paradigm was repeated in two identical neuroimaging sessions with intravenous infusions of either low-dose remifentanil (0.7ng/ml target-controlled infusion) or saline (randomised). During saline infusion, breathlessness anticipation activated the right anterior insula and the adjacent operculum. Breathlessness was associated with activity in a network including the insula, operculum, dorsolateral prefrontal cortex, anterior cingulate cortex and the primary sensory and motor cortices. Remifentanil reduced breathlessness unpleasantness but not breathlessness intensity. Remifentanil depressed anticipatory activity in the amygdala and the hippocampus that correlated with reductions in breathlessness unpleasantness. During breathlessness, remifentanil decreased activity in the anterior insula, anterior cingulate cortex and sensory motor cortices. Remifentanil-induced reduction in breathlessness unpleasantness was associated with increased activity in the rostral anterior cingulate cortex and nucleus accumbens, components of the endogenous opioid system known to decrease the perception of aversive stimuli. These findings suggest that in addition to effects on brainstem respiratory control, opioids palliate breathlessness through an interplay of altered associative learning mechanisms. These mechanisms provide potential targets for novel ways to develop and assess treatments for chronic breathlessness.

Outcomes of Hip Arthroplasty After Failed Hip Arthroscopy: A Case-Control Study.

BACKGROUND: Hip arthroscopy is increasingly being used in joint preservation surgery with clear benefits in the treatment of prearthritic conditions. A number of patients, however, will still go on to require subsequent hip arthroplasty, and at present, little evidence exists determining the impact that prior hip arthroscopy may have on the outcomes of a subsequent arthroplasty. METHODS: Using prospectively collated data, we identified 35 patients who had a hip arthroplasty (22 total hip arthroplasties and 13 hip resurfacing arthroplasties) after prior ipsilateral hip arthroscopy (cases). Cases were matched for age, gender, and prosthesis type with 70 controls (patients who received a primary arthroplasty over the same period, without prior arthroscopy). Outcome measures included range of movement, implant survival, complications, and functional outcome (Oxford Hip Score and Harris Hip Score). RESULTS: There was no demonstrable difference in improved range of motion after hip arthroplasty between the 2 groups, across any axis of movement (flexion, extension, internal/external rotation, abduction, and adduction; P = .07-.78). There was no significant difference in complication rate (P = .72). Overall 7-year implant survival was 85.9% (95% confidence interval [CI], 75-95.8). There was no difference in survival between cases (87.6%; 95% CI, 73.5-100) and controls (86.3%; 95% CI, 74.6%-98.0%; P = .2). Ten of the 11 revision arthroplasties performed were due to adverse reactions to metal debris in metal-on-metal hip resurfacing arthroplasty cases (P = .01). There was no difference in improvement of functional outcome postarthroplasty between groups (P = .48-.76). CONCLUSION: This study demonstrates that hip arthroscopy does not adversely influence outcome of a subsequent hip arthroplasty.

Remote effects of acute kidney injury in a porcine model.

Acute kidney injury (AKI) is a common and serious condition with no specific treatment. An episode of AKI may affect organs distant from the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we tested the hypothesis that early effects of AKI on distant organs is by immune cell infiltration, leading to inflammatory cytokine production, extravasation, and edema. In 29 pigs exposed to either sham surgery or renal ischemia-reperfusion (control, n = 12; AKI, n = 17), we assessed remote organ (liver, lung, brain) effects in the short (from 2- to 48-h reperfusion) and longer term (5 wk later) using immunofluorescence (for leukocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (e.g., electrolytes), blood hematology and chemistry (e.g., liver enzymes), and PCR (for inflammatory markers). AKI elicited significant, short-term (∼24 h) increments in enzymes indicative of acute liver damage (e.g. , AST: ALT ratio; P = 0.02) and influenced tissue biochemistry in some remote organs (e.g., lung tissue [Ca(2+)] increased; P = 0.04). These effects largely resolved after 48 h, and no further histopathology, edema, apoptosis, or immune cell infiltration was noted in the liver, lung, or hippocampus in the short and longer term. AKI has subtle biochemical effects on remote organs in the short term, including a transient increment in markers of acute liver damage. These effects resolved by 48 h, and no further remote organ histopathology, apoptosis, edema, or immune cell infiltration was noted.

Association between depression and anemia in otherwise healthy adults.

OBJECTIVE: It remains debated whether anemia is associated with depression, independently of physical health factors. We report a large-scale cross-sectional study examining this association in adults free of chronic disease and medication from the general population. METHOD: Hemoglobin levels were measured among 44 173 healthy participants [63% men; mean [standard deviation] age = 38.4 (11.1) years] from the 'Investigations Préventives et Cliniques' (IPC) cohort study. Depression was measured with the Questionnaire of Depression 2nd version, Abridged. Logistic regression analyses were performed to examine the association between anemia and depression, while adjusting for a wide range of sociodemographic characteristics and health-related factors (i.e., sex, age, living status, education level, occupational status, alcohol intake, smoking status, physical activity, and body mass index). RESULTS: Depressed participants were significantly more likely to have anemia compared to non-depressed participants, even after adjustment for sociodemographic and health-related variables [odds ratio = 1.36; 95% confidence interval = (1.18; 1.57)]. Anemia prevalence increased with depression severity, suggesting a dose-response relationship (P for trend <0.001). CONCLUSION: In healthy adults from the general population, we found a significant and robust association between depression and anemia. Further studies are needed to assess the longitudinal relationship between both conditions and determine the mechanisms underlying this association.

Calculation of the chemical potential and the activity coefficient of two layers of CO2 adsorbed on a graphite surface.

We study the adsorption of carbon dioxide at a graphite surface using the new Small System Method, and find that for the temperature range between 300 K and 550 K most relevant for CO2 separation; adsorption takes place in two distinct thermodynamic layers defined according to Gibbs. We calculate the chemical potential and the activity coefficient of both layers directly from the simulations. Based on thermodynamic relations, the entropy and enthalpy of the CO2 adsorbed layers are also obtained. Their values indicate that there is a trade-off between entropy and enthalpy when a molecule chooses for one of the two layers. The first layer is a densely packed monolayer of relatively constant excess density with relatively large repulsive interactions and negative enthalpy. The second layer has an excess density varying with the temperature, an activity coefficient, which also indicates repulsion, but to a much smaller degree than in the first layer. Results for activity coefficients, entropies and enthalpies can be used to model transport through and along graphitic membranes for carbon dioxide separation purposes.

Characterization of adsorbed water in MIL-53(Al) by FTIR spectroscopy and ab-initio calculations.

Here, we report ab-initio calculations developed with a twofold purpose: understand how adsorbed water molecules alter the infrared spectrum of the metal-organic framework MIL-53(Al) and to investigate which are the associated physico-chemical processes. The analyzed structures are the two anhydrous narrow (np⊘) and large (lp⊘) pore forms and the hydrated narrow pore form (np-H2O) of the MIL-53(Al). For these structures, we determined their corresponding infrared spectra (FTIR) and we identified the vibrational modes associated to the dominant spectral lines. We show that wagging and scissoring modes of CO2 give flexibility to the structure for facilitating the lp⊘- np⊘ transition. In our studies, this transition is identified by eight vibrational modes including the δCH(18a) vibrational mode currently used to identify the mentioned transition. We report an exhaustive band identification of the infrared spectra associated to the analyzed structures. Moreover, the FTIR for the np-H2O structure allowed us to identify four types of water molecules linked to the host structure by one to three hydrogen bonds.

Remote conditioning or erythropoietin before surgery primes kidneys to clear ischemia-reperfusion-damaged cells: a renoprotective mechanism?

Acute kidney injury is common, serious with no specific treatment. Ischemia-reperfusion is a common cause of acute kidney injury (AKI). Clinical trials suggest that preoperative erythropoietin (EPO) or remote ischemic preconditioning may have a renoprotective effect. Using a porcine model of warm ischemia-reperfusion-induced AKI (40-min bilateral cross-clamping of renal arteries, 48-h reperfusion), we examined the renoprotective efficacy of EPO (1,000 iu/kg iv.) or remote ischemic preconditioning (3 cycles, 5-min inflation/deflation to 200 mmHg of a hindlimb sphygmomanometer cuff). Ischemia-reperfusion induced significant kidney injury at 24 and 48 h (χ(2), 1 degree of freedom, >10 for 6/7 histopathological features). At 2 h, a panel of biomarkers including plasma creatinine, neutrophil gelatinase-associated lipocalin, and IL-1ß, and urinary albumin:creatinine could be used to predict histopathological injury. Ischemia-reperfusion increased cell proliferation and apoptosis in the renal cortex but, for pretreated groups, the apoptotic cells were predominantly intratubular rather than interstitial. At 48-h reperfusion, plasma IL-1ß and the number of subcapsular cells in G2-M arrest were reduced after preoperative EPO, but not after remote ischemic preconditioning. These data suggest an intrarenal mechanism acting within cortical cells that may underpin a renoprotective function for preoperative EPO and, to a limited extent, remote ischemic preconditioning. Despite equivocal longer-term outcomes in clinical studies investigating EPO as a renoprotective agent in AKI, optimal clinical dosing and administration have not been established. Our data suggest further clinical studies on the potential renoprotective effect of EPO and remote ischemic preconditioning are justified.

Hypofractionated postoperative stereotactic radiotherapy for large resected brain metastases.

PURPOSE: The aim of the present retrospective study was to report outcomes after hypofractionated stereotactic radiotherapy (HSRT) for resected brain metastases (BM). PATIENTS AND METHODS: We reviewed results of patients with resected BM treated with postoperative HSRT (3×7.7Gy to the prescription isodose 70%) between May 2013 and June 2020. Local control (LC), distant brain control (DBC), overall survival (OS), leptomeningeal disease relapse (LMDR), and radiation necrosis (RN) occurrence were reported. RESULTS: Twenty-two patients with 23 brain cavities were included. Karnofsky Performance status (KPS) was≥70 in 77.3%. Median preoperative diameter was 37mm [21.0-75.0] and median planning target volume (PTV) was 23 cm3 [9.9-61.6]. Median time from surgery to SRT was 69 days [7-101] and 48% of patients had a local relapse on pre-SRT imaging. Median follow-up was 17.5 months [1.6-95.9]. One and two-year LC rates were 60.9 and 52.2% respectively. One and 2-year DBC rates were 45.5 and 40.9%. Median OS was 16.5 months. Four patients (18.2%) presented LMDR during follow-up. RN occurred in 6 patients (27.2%). Three factors were associated with OS: ECOG-PS (P=0.009), KPS (P=0.04), cystic or solid nature of the metastasis before surgery (P=0.037). Several factors were related to RN occurrence: PTV diameter and volume, Normal brain V21, V21 and V24 isodoses volumes. CONCLUSION: HSRT is the most widely used scheme for larger brain cavities after surgery. The optimal dose and scheme remain to be defined as well as the optimal delay between postoperative SRT and surgery. Dose escalation may be necessary, especially in case of subtotal resection.

[Efficacy and tolerance of salvage curative radiotherapy for patients with cervical relapse of differentiated thyroid carcinoma]. / Efficacité et tolérance de la radiothérapie externe pour les patients atteints d'une récidive d'un carcinome différencié de la thyroïde.

PURPOSE: Radiation therapy is often the last resource treatment for cervical relapse in iodine refractory differentiated thyroid cancer. We present locoregional control data in patients with cervical relapse treated with curative intent radiation therapy with or without concomitant carboplatin. MATERIAL AND METHODS: This monocentric retrospective study gathered data on patients with differentiated thyroid carcinoma - vesicular or papillary - in relapse after thyroidectomy who received a curative intent cervical radiation therapy. Locoregional progression free survival (LRPFS), progression free survival (PFS), overall survival (OS) were gathered as well as acute and chronic adverse events assessed with the CTCAE v4. RESULTS: Thirty-nine patients were consecutively included between 2005 and 2019. The median follow-up was 36.6months. Fifteen patients (38%) had a locoregional relapse, locoregional control at 2years was 66.7%. The median LRPFS was 48months [32.9-not reached] and the median overall survival 49months [38.8-not reached]. In multivariate analysis, initial incomplete resection was associated with poorer OS (HR: 24.39 [3.57-166.78], P=0.00113) and LRPFS (HR: 33.91 [4.46-257.61], P=0.00066), extra nodal spread was associated with poorer LRPFS (HR: 13.45 [1.81-99,76], P=0.011). ECOG performance status was associated with OS (HR: 5.11 [1.57-16.66], P=0.00688). Carboplatin association with radiation therapy was not associated with improved survivals (OS: P=0.34, LRPFS: P=0.84). The rate of acute grade 3 toxicities was 14%. CONCLUSION: Salvage cervical radiation therapy was associated with a locoregional control of 66.7% at 2years with a reasonable toxicity rate. Carboplatin association with radiation therapy did not improve locoregional control nor overall survival in comparison with radiotherapy alone.

Optic nerve motion and gaze direction: Their impact on intraorbital tumor radiotherapy.

PURPOSE: Management of inter- and intra-fraction movements of target volumes and organs at risk (OARs) during radiotherapy is essential. While there is little OAR or target volume movement, the movements and orientation of the eyes can be significant during radiotherapy and they can affect the position of the optic nerve. The objective of the present study was to assess the variations of the optic nerve position due to gaze direction and to discuss their clinical consequences on the radiation treatment of intraorbital tumors. MATERIAL AND METHODS: Three patients without a history of oculomotor nerve palsy underwent six CT acquisitions with a thermoplastic mask: eyes open with different gaze directions (straight ahead, left, right, up, down) and eyes closed. The acquisition with the straight-ahead gaze was chosen as the reference position. Left and right optic nerves were segmented on the six acquisitions, and total volumes and maximum amplitude motions were calculated in three dimensions. RESULTS: Maximum differences were observed while looking left and up, with a median maximum amplitude of 5 and 6mm [range: 2-7mm], respectively. These motions induced a position variation of more than 50% of the volume of the optic nerve (compared to the reference position). Greater variations of motion were observed for the anterior portion of the nerve. The gaze position with the fewest variations compared to the reference position was eyes closed. CONCLUSION: Optic nerve positions vary significantly due to the gaze direction, especially for the anterior portion of the nerve. These variations should be taken into account for the treatment of small intraorbital tumors involving the anterior third of the optic nerve.

Protein restriction in the pregnant mouse modifies fetal growth and pulmonary development: role of fetal exposure to {beta}-hydroxybutyrate.

Maternal undernutrition during sensitive periods of pregnancy results in offspring predisposed towards the development of a number of diseases of adulthood, including hypertension and diabetes. In order to determine the nature of any gross alterations in fetal growth during early organogenesis, we supplied timed-mated pregnant mice with diets containing 6% protein (6%P), 9% protein (9%P) or 18% protein (18%P; control) from day 0 of pregnancy. At embryonic days 11 (E11), 12 (E12) and 13 (E13), females were killed and fetuses removed. Gross morphological analysis revealed that fetal limb growth was impaired between E11 and E12 in 6%P animals, but this recovered by E13. Likewise, fetal liver growth and lung branching morphogenesis were seen to exhibit an initial growth impairment at E12 followed by a rapid recovery by E13. Coincident with the observed changes in fetal growth, we noted an elevation in maternal hepatic triglyceride content, expression of the ketogenic 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) and circulating plasma ß-hydroxybutyrate (BOHB). In addition, fetal liver Hmgcs2 expression was switched on by E13 in both 6%P- and 9%P-exposed animals. Exogenous BOHB did not influence branching morphogenesis in fetal lung explant cultures; however, we cannot rule out the possibility that this may occur in vivo. In conclusion, we find that disturbance of fetal growth by maternal dietary protein restriction is associated and therefore potentially indicated by changes in maternal and fetal ketone body metabolism.