Aperiodic neural activity is a biomarker for depression severity.

A reliable physiological biomarker for Major Depressive Disorder (MDD) is necessary to improve treatment success rates by shoring up variability in outcome measures. In this study, we establish a passive biomarker that tracks with changes in mood on the order of minutes to hours. We record from intracranial electrodes implanted deep in the brain - a surgical setting providing exquisite temporal and spatial sensitivity to detect this relationship in a difficult-to-measure brain area, the ventromedial prefrontal cortex (VMPFC). The aperiodic slope of the power spectral density captures the balance of activity across all frequency bands and is construed as a putative proxy for excitatory/inhibitory balance in the brain. This study demonstrates how shifts in aperiodic slope correlate with depression severity in a clinical trial of deep brain stimulation for treatment-resistant depression (TRD). The correlation between depression severity scores and aperiodic slope is significant in N=5 subjects, indicating that flatter (less negative) slopes correspond to reduced depression severity, especially in the ventromedial prefrontal cortex. This biomarker offers a new way to track patient response to MDD treatment, facilitating individualized therapies in both intracranial and non-invasive monitoring scenarios.

Association of glucose metabolism and blood pressure during pregnancy with subsequent maternal blood pressure.

The goal of this study was to examine associations of measures of maternal glucose metabolism and blood pressure during pregnancy with blood pressure at follow-up in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. The HAPO Follow-Up Study included 4747 women who had a 75-g oral glucose tolerance test (OGTT) at ~28 weeks' gestation. Of these, 4572 women who did not have chronic hypertension during their pregnancy or other excluding factors, had blood pressure evaluation 10-14 years after the birth of their HAPO child. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (SBP ≥ 140 and/or DBP ≥ 90 or treatment for hypertension) at follow-up. Blood pressure during pregnancy was associated with all blood pressure outcomes at follow-up independent of glucose and insulin sensitivity during pregnancy. The sum of glucose z-scores was associated with blood pressure outcomes at follow-up but associations were attenuated in models that included pregnancy blood pressure measures. Associations with SBP were significant in adjusted models, while associations with DBP and hypertension were not. Insulin sensitivity during pregnancy was associated with all blood pressure outcomes at follow-up, and although attenuated after adjustments, remained statistically significant (hypertension OR 0.79, 95%CI 0.68-0.92; SBP beta -0.91, 95% CI -1.34 to -0.49; DBP beta -0.50, 95% CI -0.81 to -0.19). In conclusion, maternal glucose values at the pregnancy OGTT were not independently associated with maternal blood pressure outcomes 10-14 years postpartum; however, insulin sensitivity during pregnancy was associated independently of blood pressure, BMI, and other covariates measured during pregnancy.

Fingerprints of Heavy-Element Nucleosynthesis in the Late-Time Lightcurves of Kilonovae.

The kilonova emission observed following the binary neutron star merger event GW170817 provided the first direct evidence for the synthesis of heavy nuclei through the rapid neutron capture process (r process). The late-time transition in the spectral energy distribution to near-infrared wavelengths was interpreted as indicating the production of lanthanide nuclei, with atomic mass number A≳140. However, compelling evidence for the presence of even heavier third-peak (A≈195) r-process elements (e.g., gold, platinum) or translead nuclei remains elusive. At early times (∼days) most of the r-process heating arises from a large statistical ensemble of ß decays, which thermalize efficiently while the ejecta is still dense, generating a heating rate that is reasonably approximated by a single power law. However, at later times of weeks to months, the decay energy input can also possibly be dominated by a discrete number of α decays, ^{223}Ra (half-life t_{1/2}=11.43 d), ^{225}Ac (t_{1/2}=10.0 d, following the ß decay of ^{225}Ra with t_{1/2}=14.9 d), and the fissioning isotope ^{254}Cf (t_{1/2}=60.5 d), which liberate more energy per decay and thermalize with greater efficiency than ß-decay products. Late-time nebular observations of kilonovae which constrain the radioactive power provide the potential to identify signatures of these individual isotopes, thus confirming the production of heavy nuclei. In order to constrain the bolometric light to the required accuracy, multiepoch and wideband observations are required with sensitive instruments like the James Webb Space Telescope. In addition, by comparing the nuclear heating rate obtained with an abundance distribution that follows the solar r abundance pattern, to the bolometric lightcurve of AT2017gfo, we find that the yet-uncertain r abundance of ^{72}Ge plays a decisive role in powering the lightcurve, if one assumes that GW170817 has produced a full range of the solar r abundances down to mass number A∼70.

Understanding longer-term disability outcomes for Maori and non-Maori after hospitalisation for injury: results from a longitudinal cohort study.

OBJECTIVES: The objectives are to (1) describe disability outcomes at 24 months after injury and (2) identify factors contributing to disability outcomes at 24 months after injury, for Maori and non-Maori who have been hospitalised for injury. STUDY DESIGN: This is a prospective cohort study. METHODS: Prospective Outcomes of Injury Study participants were injured New Zealanders aged 18-64 years and recruited from New Zealand's no-fault injury insurer, the Accident Compensation Corporation's entitlement claims register. Data about a number of pre-injury, injury-related and early post-injury characteristics were collected from interviews held at 3 and 24 months after injury. Disability was measured using the World Health Organization Disability Assessment Schedule (WHODAS). Modified Poisson regression modelling was used to estimate relative risks (RRs) of disability for Maori and non-Maori who were hospitalised for injury. RESULTS: Analyses were restricted to 375 Maori and 1824 non-Maori participants for whom complete data were available. Of these, 105 (28%) Maori and 446 (24%) non-Maori were hospitalised for their injury. Of these hospitalised groups, 26% of Maori and 10% of non-Maori were experiencing disability (WHODAS ≥10) at 24 months after injury. Maori who were hospitalised for injury and who were not working for pay before their injury (RR = 2.7; 95% confidence interval [CI] 1.4-4.9), who were experiencing disability before their injury (RR = 3.1; 95% CI 1.6-5.8) or who reported trouble accessing healthcare services for their injury (RR = 2.6; 95% CI 1.3-5.2) were independently at increased risk of disability 24 months after injury. Non-Maori who were hospitalised for injury and who had inadequate household income before injury (RR = 2.4; 95% CI 1.4-4.1), less than the secondary school qualifications (RR = 2.0; 95% CI 1.1-3.8), were not working for pay before injury (RR = 2.8; 95% CI 1.5-5.1), were experiencing disability before their injury (RR = 3.0; 95% CI 1.7-5.2), had ≥2 chronic conditions (RR = 3.5; 95% CI 2.0-6.4) or had body mass index ≥30 kg/m2/undisclosed (RR = 2.4; 95% CI 1.3-4.4) were at increased risk of disability 24 months after injury. CONCLUSIONS: Variables predicting disability 24 months after injury for Maori, also predict disability 24 months after injury for non-Maori, with one notable exception-trouble accessing healthcare services. Our findings show that having access to healthcare services for injury plays an important role after injury and must be focussed on to ensure that the burden of poor injury-related outcomes and injury-related inequities are reduced and ultimately eliminated.

X-Rays from the Location of the Double-humped Transient ASASSN-15lh.

We present the detection of persistent soft X-ray radiation with Lx ~ 1041-1042 erg s-1 at the location of the extremely luminous, double-humped transient ASASSN-15lh as revealed by Chandra and Swift. We interpret this finding in the context of observations from our multiwavelength campaign, which revealed the presence of weak narrow nebular emission features from the host-galaxy nucleus and clear differences with respect to superluminous supernova optical spectra. Significant UV flux variability on short timescales detected at the time of the rebrightening disfavors the shock interaction scenario as the source of energy powering the long-lived UV emission, while deep radio limits exclude the presence of relativistic jets propagating into a low-density environment. We propose a model where the extreme luminosity and double-peaked temporal structure of ASASSN-15lh is powered by a central source of ionizing radiation that produces a sudden change in the ejecta opacity at later times. As a result, UV radiation can more easily escape, producing the second bump in the light curve. We discuss different interpretations for the intrinsic nature of the ionizing source. We conclude that, if the X-ray source is physically associated with the optical-UV transient, then ASASSN-15lh most likely represents the tidal disruption of a main-sequence star by the most massive spinning black hole detected to date. In this case, ASASSN-15lh and similar events discovered in the future would constitute the most direct probes of very massive, dormant, spinning, supermassive black holes in galaxies. Future monitoring of the X-rays may allow us to distinguish between the supernova hypothesis and the hypothesis of a tidal disruption event.

Gravitational-wave localization alone can probe origin of stellar-mass black hole mergers.

The recent discovery of gravitational waves from stellar-mass binary black hole mergers by the Laser Interferometer Gravitational-wave Observatory opened the door to alternative probes of stellar and galactic evolution, cosmology and fundamental physics. Probing the origin of binary black hole mergers will be difficult due to the expected lack of electromagnetic emission and limited localization accuracy. Associations with rare host galaxy types-such as active galactic nuclei-can nevertheless be identified statistically through spatial correlation. Here we establish the feasibility of statistically proving the connection between binary black hole mergers and active galactic nuclei as hosts, even if only a sub-population of mergers originate from active galactic nuclei. Our results are the demonstration that the limited localization of gravitational waves, previously written off as not useful to distinguish progenitor channels, can in fact contribute key information, broadening the range of astrophysical questions probed by binary black hole observations.Binary black hole mergers have recently been observed through the detection of gravitational wave signatures. The authors demonstrate that their association with active galactic nuclei can be made through a statistical spatial correlation.

Excessive gestational weight gain in the first trimester among women with normal glucose tolerance and resulting neonatal adiposity.

OBJECTIVE: To assess whether weight gain above or below Institute of Medicine (IOM) recommended amounts in an ethnically diverse obstetric population with normal glucose tolerance is associated with differences in neonatal adiposity. STUDY DESIGN: In this prospective cohort study, healthy women with normal glucose tolerance based on the International Association of Diabetes and Pregnancy Study Groups guidelines were enrolled. Gestational weight at multiple time points were collected. Neonatal adiposity was measured by air displacement plethysmography at 24 to 72 h of life. Analyses included Fisher's exact test, analysis of variance and a trajectory analysis using a group-based weight gain trajectory model with a censored normal distribution. RESULTS: Overweight and obese women were more likely to exceed IOM weight gain guidelines. Regardless, there was no significant difference in %body fat of neonates born to mothers who either met or exceeded gestational weight gain (GWG) guidelines. GWG timing influenced neonatal anthropometrics: women who gained excessively by the first prenatal visit had neonates with significantly higher birth weight (3.91 vs 3.45 kg, P<0.001) and %body fat (13.7 vs 10.9%, P=0.0001) compared with women who had steady and moderate GWG. CONCLUSION: Avoidance of excessive GWG in the first trimester may prevent high amounts of neonatal adiposity.

A radio jet from the optical and x-ray bright stellar tidal disruption flare ASASSN-14li.

The tidal disruption of a star by a supermassive black hole leads to a short-lived thermal flare. Despite extensive searches, radio follow-up observations of known thermal stellar tidal disruption flares (TDFs) have not yet produced a conclusive detection. We present a detection of variable radio emission from a thermal TDF, which we interpret as originating from a newly launched jet. The multiwavelength properties of the source present a natural analogy with accretion-state changes of stellar mass black holes, which suggests that all TDFs could be accompanied by a jet. In the rest frame of the TDF, our radio observations are an order of magnitude more sensitive than nearly all previous upper limits, explaining how these jets, if common, could thus far have escaped detection.

The chromosome 3q25 locus associated with fetal adiposity is not associated with childhood adiposity.

Increased newborn adiposity is associated with later adverse metabolic outcomes. Previous genome-wide association studies (GWAS) demonstrated strong association of a locus on chromosome 3 (3q25.31) with newborn sum of skinfolds, a measure of overall adiposity. Whether this locus is associated with childhood adiposity is unknown. Genotype and sum of skinfolds data were available for 293 children at birth and age 2, and for 350 children at birth and age 6 from a European cohort (Belfast, UK) who participated in the Hyperglycemia and Adverse Pregnancy Outcome GWAS. We examined single nucleotide polymorphisms (SNPs) at the 3q25.31 locus associated with newborn adiposity. Linear regression analyses under an additive genetic model adjusting for maternal body mass index were performed. In both cohorts, a positive association was observed between all SNPs and sum of skinfolds at birth (P=2.3 × 10(-4), ß=0.026 and P=4.8 × 10(-4), ß=0.025). At the age of 2 years, a non-significant negative association was observed with sum of skinfolds (P=0.06; ß =-0.015). At the age of 6 years, there was no evidence of association (P=0.86; ß=0.002). The 3q25.31 locus strongly associated with newborn adiposity had no significant association with childhood adiposity suggesting that its impact may largely be limited to fetal fat accretion.

Prevalence and molecular characterization of Hepatozoon canis in dogs from urban and rural areas in Southeast Brazil.

The objective of this survey was to investigate the prevalence of Hepatozoon infection in dogs in the rural and urban areas of Uberlândia, Brazil by PCR and molecular characterization. DNA was obtained from blood samples collected from 346 local dogs from both genders and various ages. Seventeen PCR products from positive blood samples of urban dogs and 13 from the rural dogs were sequenced. Partial sequences of the 18S rRNA gene indicated that all 30 dogs were infected with Hepatozoon canis similar in sequence to H. canis from southern Europe. Four local dog sequences were submitted to GenBank (accessions JN835188; KF692038; KF692039; KF692040). This study indicates that H. canis is the cause of canine hepatozoonosis in Uberlândia and that infection is similarly widespread in rural and urban dogs.

Eddy viscosity in dense granular flows.

We present a seminal set of experiments on dense granular flows in the stadium shear geometry. The advantage of this geometry is that it produces steady shear flow over large deformations, in which the shear stress is constant. The striking result is that the velocity profiles exhibit an S shape, and are not linear as local constitutive laws would predict. We propose a model that suggests this is a result of wall perturbations which span through the system due to the nonlocal behavior of the material. The model is analogous to that of eddy viscosity in turbulent boundary layers, in which the distance to the wall is introduced to predict velocity profiles. Our findings appear pivotal in a number of experimental and practical situations involving dense granular flows next to a boundary. They could further be adapted to other similar materials such as dense suspensions, foams, or emulsions.

Maternal testosterone levels are associated with C-peptide levels in the Mexican American subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study cohort.

Altered sex hormone levels are thought to play an important role in adult-onset diseases including obesity, cardiovascular disease, and diabetes. They contribute to these complex diseases through changes in their availability, which is influenced, in part, by binding proteins. Insulin resistance, which is characteristic of these diseases, along with increased insulin secretion, is a physiologic change that occurs normally during pregnancy. To determine the relationship between insulin resistance and sex hormone levels, we examined the associations of sex hormone-binding globulin (SHBG) and testosterone with measures of glycemia and insulinemia in a healthy pregnant population. We measured fasting serum SHBG and testosterone levels in 215 Hispanic mothers of Mexican ancestry from the HAPO Study cohort and tested for associations between SHBG and testosterone levels and maternal plasma glucose and C-peptide. After adjusting for confounding variables, serum total testosterone (TT) was positively associated with fasting C-peptide (0.18 µg/l higher for TT higher by 1 SD, p=0.001) and 1-h C-peptide (0.79 µg/l higher for TT higher by 1 SD, p<0.001). Free testosterone (FT) was also positively associated with fasting C-peptide (0.19 µg/l higher for FT higher by 1 SD, p<0.001), and 1-h C-peptide (0.83 µg/l higher for FT higher by 1 SD, p<0.001). Although these findings are from a single cohort, this study provides evidence for an association between testosterone and C-peptide during pregnancy in a nondiabetic Hispanic obstetric population.

Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity.

BACKGROUND: More than 40% of women with a normal pre-pregnancy body mass index (BMI) exceed the 2009 Institute of Medicine (IOM) guidelines' recommended weight gain of 25-35 lb. Excessive gestational weight gain is one modifiable factor that may be contributing to childhood overweight and obesity. OBJECTIVE: The objective of this study was to evaluate differences in adiposity from neonates born to mothers with a normal pre-pregnancy BMI who either gained within or above IOM guidelines. METHODS: Neonatal adiposity was measured within 72 h of birth by the method of air displacement plethysmography. RESULTS: Compared with mothers who gained within IOM guidelines (N = 27), mothers with excessive gestational weight gain (N = 11) (mean 29.0 vs. 45.2 lb) had neonates with 50% more fat mass (348 vs. 525 g) and 3% greater body fat (10.7 vs. 13.9%). CONCLUSIONS: Increased adiposity at birth may predispose these children to increased risk of obesity and highlight the importance that women avoid gaining excessive weight in pregnancy.

A faint type of supernova from a white dwarf with a helium-rich companion.

Supernovae are thought to arise from two different physical processes. The cores of massive, short-lived stars undergo gravitational core collapse and typically eject a few solar masses during their explosion. These are thought to appear as type Ib/c and type II supernovae, and are associated with young stellar populations. In contrast, the thermonuclear detonation of a carbon-oxygen white dwarf, whose mass approaches the Chandrasekhar limit, is thought to produce type Ia supernovae. Such supernovae are observed in both young and old stellar environments. Here we report a faint type Ib supernova, SN 2005E, in the halo of the nearby isolated galaxy, NGC 1032. The 'old' environment near the supernova location, and the very low derived ejected mass ( approximately 0.3 solar masses), argue strongly against a core-collapse origin. Spectroscopic observations and analysis reveal high ejecta velocities, dominated by helium-burning products, probably excluding this as a subluminous or a regular type Ia supernova. We conclude that it arises from a low-mass, old progenitor, likely to have been a helium-accreting white dwarf in a binary. The ejecta contain more calcium than observed in other types of supernovae and probably large amounts of radioactive (44)Ti.

The role of the polycystic ovary syndrome susceptibility locus D19S884 allele 8 in maternal glycemia and fetal size.

CONTEXT: The high incidence of insulin resistance, type 2 diabetes, and metabolic syndrome in Western societies and their impact on quality of life emphasize the importance of identifying underlying susceptibility loci for metabolic diseases. The polycystic ovary syndrome (PCOS) susceptibility locus D19S884 allele 8 (A8) is associated with measures of insulin resistance, beta-cell dysfunction, and other metabolic phenotypes in PCOS families. We now investigate the role of D19S884 A8 in pregnancy. OBJECTIVE: Using the multiethnic Hyperglycemia and Adverse Pregnancy Outcome cohort, we assessed the associations of D19S884 A8 with measures of maternal glycemia and fetal size. DESIGN: We tested for association of maternal D19S884 A8 with maternal outcomes (fasting, 1-h, and 2-h plasma glucose, and fasting and 1-h C-peptide from an oral glucose tolerance test) and fetal and maternal D19S884 A8 with fetal outcomes (birth weight, length, head circumference, sum of skin folds, fat mass, cord C-peptide, and 2-h neonatal plasma glucose). SUBJECTS: We analyzed 4424 Caucasian mothers and 3347 offspring of northern European ancestry, 1957 Thai mothers and 2089 offspring from Bangkok, 1208 Afro-Caribbean mothers and 1209 offspring from Barbados, and 774 Hispanic mothers and 762 offspring from Bellflower, California. RESULTS: After adjusting for confounding variables and multiple testing, neither maternal nor fetal D19S884 A8 showed significant evidence for association with any of the outcomes tested. CONCLUSIONS: The PCOS susceptibility locus, D19S884 A8, is not a major factor contributing to glycemia during pregnancy or fetal size in a general obstetric population.

A comparison of pectin, polyphenols, and phytosterols, alone or in combination, to lovastatin for reduction of serum lipids in familial hypercholesterolemic swine.

Greater than 50% of Americans use some form of a dietary supplement, and a diagnosis of coronary artery disease is associated with higher supplement use. The objective of this study was to compare nutritional supplements (pectin, polyphenols, and phytosterols) to lovastatin to reduce serum cholesterol. Familial hypercholesterolemic (FH) swine received the same amount of basal diet (control) in addition to pectin (30 g/day), polyphenols (20 g/day), phytosterols (6 g/day), and all possible combinations in contrast to lovastatin (3 mg/kg of body weight). The experimental design consisted of 4 weeks of basal diet followed by 4 weeks of basal diet plus the supplement treatment. All of the supplements, except pectin, reduced total cholesterol by an average of 71 +/- 19 mg/dL in comparison to the control diet (53 +/- 20 mg/dL) and lovastatin (143 +/- 21 mg/dL) during the 5-8-week treatment period. Serum high-density lipoprotein-cholesterol remained unchanged, while serum triglycerides changed independent of diet. During the 5-8-week treatment period serum low-density lipoprotein (LDL)-cholesterol was reduced maximally 22%, 19%, 20%, 17%, 18%, and 17% by polyphenols, phytosterols, pectin + polyphenols, pectin + phytosterols, polyphenols + phytosterols, and pectin + polyphenols + phytosterols, respectively, compared to control (8%) and lovastatin (40%). Phytosterols was the most effective supplementation, while both phytosterol and polyphenol supplements enhanced the reduction in LDL-cholesterol of pectin-containing diets. Supplements effectively reduced cholesterol in FH swine by half compared to lovastatin. Results suggest that more research on the use of dietary supplements, alone or in combination with statins, to reduce LDL-cholesterol is justified.

Comparative single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following a new dual-release and a conventional slow-release formulation of levodopa and benserazide in healthy volunteers.

The objective was to assess the single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following administration of a new dual-release and conventional slow-release formulation of levodopa/benserazide in the dose ratio of 4:1. In an open-label, two-way cross-over study, 20 healthy volunteers were randomized to receive first either Madopar DR or Madopar HBS for 8 days. Then they crossed over to the other formulation. A first dose of 200 mg levodopa and 50 mg benserazide ('250' mg) was given on day 1, '125' mg t.i.d. on the subsequent 6 days (days 2-7), followed by '250' mg on day 8. The two treatment periods of 8 days were separated by a wash-out period of at least 7 days. Blood samples were taken at specific times over a 12-hour period (day 1) or a 36-hour period (day 8). Plasma concentrations of levodopa and 3-O-methyldopa were measured by high-performance liquid chromatography for pharmacokinetic evaluation. The pharmacokinetics of levodopa after a single-dose administration (day 1) of Madopar DR and Madopar HBS were significantly different as reflected by the respective mean values of maximum plasma concentration (C(max) 1.99 vs. 0.82 mg x l-1), time to reach maximum concentration (t(max) 0.7 vs. 2.6 h) and area under the plasma concentration-time curve (AUC(0- infinity ) 4.52 vs. 3.18 mg x h x l-1). The respective values after multiple doses (day 8) were: C(max) 1.98 vs. 0.93 mg x l-1, t(max) 0.7 vs. 2.3 h and AUC(0-infinity ) 4.84 vs. 3.96 mg x h x l-1. The relative bioavailability (Madopar DR vs. Madopar HBS) was 1.73 on day 1 and 1.32 on day 8. Bioequivalence could not be demonstrated for log-transformed data of AUC and C(max) within a predefined range of 80-125 and 70-143%, respectively. In conclusion, the observed differences in C(max), t(max) and AUC are consistent with a faster rate and higher extent of levodopa absorption after administration of Madopar DR. Statistical evaluation of these kinetic data showed that Madopar DR is not bioequivalent to Madopar HBS.

Declining insulin requirement in the late first trimester of diabetic pregnancy.

OBJECTIVE: To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin requirement. RESEARCH DESIGN AND METHODS: We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic women in the Diabetes in Early Pregnancy Study (DIEP) with accurate gestational dating, regular glucose monitoring, daily insulin-dose recording, and monthly glycohemoglobin measurements. RESULTS: In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was observed between weeks 3 and 7 (P = 0.000), followed by a significant 9% decline from week 7 through week 15 (P = 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7-8 and ending weeks 11-12 (P = 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and 11 (median), and 8 and 9 (most frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women based on their glycohemoglobin values: <2 SDs above the mean of a normal population (subgroup 1), 2-4 SDs (subgroup 2), and >4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 (P = 0.002) and subgroups 2 and 3 together (P = 0.003). Similarly, women with BMI >27.0 had a greater initial insulin rise and then fall compared with leaner women. CONCLUSIONS: Observations in the DIEP cohort disclose a mid-first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include overinsulinization of previously poorly controlled diabetes, a transient decline in progesterone secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of gestation.

Effect of genetic obesity on thermoregulatory activity responses to inversion of the light/dark cycle.

In this pilot work, the authors compared the circadian rhythm responses of 3-month-old female fatty Zucker rats with those of lean Zucker rats and Sprague-Dawley rats to reversal of the light/dark (LD) cycle. Core temperature and spontaneous cage activity were continuously monitored by implanted microtelemetry devices prior to and for 5 days following complete LD cycle reversal. By the 5th day after LD reversal, temperature rhythm nadir had phase-advanced 10.5 hours in the lean Zucker rats, 10.8 hours in the Sprague-Dawley rats, and only 3.8 hours in the fatty Zucker rats. Similarly, total activity increased in lean Zucker rats and Sprague-Dawley rats after LD reversal but declined in the fatty Zucker rat during the same time. Results of this study show that obese Zucker rats displayed an impaired ability to reentrain circadian rhythms for temperature and activity when compared to lean Zucker rats and Sprague-Dawley rats. These findings suggest that dysfunction in the circadian pacemaker previously shown to manifest itself by 43 weeks of age in fatty Zucker rats may already be present at 3 months of age and suggest that altered thermoregulation may play a role in the development of obesity in this animal model of genetic obesity.

Effects of exercise conditioning on thermoregulatory response to anticholinesterase insecticide toxicity.

Chronic exercise conditioning has been shown to alter basal thermoregulatory processes (change in thermoregulatory set point) as well as the response to infectious fever Chlorpyrifos (CHP), an organophosphate insecticide, also affects thermoregulation, causing an acute period of hypothermia followed by a delayed fever. This study examined whether chronic exercise training in the rat alters the thermoregulatory response to CHP. Core temperature and motor activity were monitored by radiotelemetry in female Sprague-Dawley rats housed individually at an ambient temperature of 22 degrees C. The rats were either given continuous access to running wheels or housed in standard cages without wheels. The exercise group ran predominately at night. After 8 weeks, the rats were gavaged with corn oil or 15 mg/kg CHP. CHP induced a transient hypothermic response followed by a delayed fever, beginning 1 day after exposure. Relative to controls, T7 decreases were not significantly different between the exercise (1.6 degrees C) group and the sedentary (0.5 degrees C) group given CHP. The sedentary and exercise group administered CHP developed a fever the day after CHP treatment. The fever response was greater in the sedentary group and persisted for approximately 3 days post-injection. Fever of the exercise group persisted for just one-half of 1 day after CHP. It is well known that chronic exercise training improves aerobic capacity; however, trained rats were not protected from the hypothermic effects of CHP. Training did ameliorate the febrile effects of CHP. Thus, exercise training may afford protection to the toxic effects of organophosphate insecticides.