Explore the vast range of titles available.

Obesity is traditionally viewed to be beneficial to bone health because of well-established positive effect of mechanical loading conferred by body weight on bone formation, despite being a risk factor for many other chronic health disorders. Although body mass has a positive effect on bone formation, whether the mass derived from an obesity condition or excessive fat accumulation is beneficial to bone remains controversial. The underline pathophysiological relationship between obesity and bone is complex and continues to be an active research area. Recent data from epidemiological and animal studies strongly support that fat accumulation is detrimental to bone mass. To our knowledge, obesity possibly affects bone metabolism through several mechanisms. Because both adipocytes and osteoblasts are derived from a common multipotential mesenchymal stem cell, obesity may increase adipocyte differentiation and fat accumulation while decrease osteoblast differentiation and bone formation. Obesity is associated with chronic inflammation. The increased circulating and tissue proinflammatory cytokines in obesity may promote osteoclast activity and bone resorption through modifying the receptor activator of NF-κB (RANK)/RANK ligand/osteoprotegerin pathway. Furthermore, the excessive secretion of leptin and/or decreased production of adiponectin by adipocytes in obesity may either directly affect bone formation or indirectly affect bone resorption through up-regulated proinflammatory cytokine production. Finally, high-fat intake may interfere with intestinal calcium absorption and therefore decrease calcium availability for bone formation. Unraveling the relationship between fat and bone metabolism at molecular level may help us to develop therapeutic agents to prevent or treat both obesity and osteoporosis. Obesity, defined as having a body mass index ≥ 30 kg/m 2 , is a condition in which excessive body fat accumulates to a degree that adversely affects health [ 1 ]. The rates of obesity rates have doubled since 1980 [ 2 ] and as of 2007, 33% of men and 35% of women in the US are obese [ 3 ]. Obesity is positively associated to many chronic disorders such as hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, and certain cancers [ 4 – 6 ]. It is estimated that the direct medical cost associated with obesity in the United States is ~$100 billion per year [ 7 ]. Bone mass and strength decrease during adulthood, especially in women after menopause [ 8 ]. These changes can culminate in osteoporosis, a disease characterized by low bone mass and microarchitectural deterioration resulting in increased bone fracture risk. It is estimated that there are about 10 million Americans over the age of 50 who have osteoporosis while another 34 million people are at risk of developing the disease [ 9 ]. In 2001, osteoporosis alone accounted for some $17 billion in direct annual healthcare expenditure. Several lines of evidence suggest that obesity and bone metabolism are interrelated. First, both osteoblasts (bone forming cells) and adipocytes (energy storing cells) are derived from a common mesenchymal stem cell [ 10 ] and agents inhibiting adipogenesis stimulated osteoblast differentiation [ 11 – 13 ] and vice versa, those inhibiting osteoblastogenesis increased adipogenesis [ 14 ]. Second, decreased bone marrow osteoblastogenesis with aging is usually accompanied with increased marrow adipogenesis [ 15 , 16 ]. Third, chronic use of steroid hormone, such as glucocorticoid, results in obesity accompanied by rapid bone loss [ 17 , 18 ]. Fourth, both obesity and osteoporosis are associated with elevated oxidative stress and increased production of proinflammatory cytokines [ 19 , 20 ]. At present, the mechanisms for the effects of obesity on bone metabolism are not well defined and will be the focus of this review.

Natural steroid hormones in the aquatic environment have attracted increasing attention because of their strong endocrine disrupting potency. Seven steroid hormones (estrone, 17α-estradiol, 17β-estradiol, estriol, testosterone, androstenedione, and progesterone) were analyzed from surface water and sediment sampled from Chaohu Lake, its upstream rivers (the Hangbu River, Nanfei River, Shiwuli River, and Pai River), drainage from the adjacent farmland, and treated and untreated municipal sewage. Concentrations of the seven target steroid hormones ranged from below the detection limit (ND) to 69.5 ng L −1 in the water of Chaohu Lake and the upstream rivers. Three steroids—estrone, estriol, and 17α-estradiol—were found in relatively high residual concentrations in the water, with maximum concentrations of 69.5 ng L −1 , 51.5 ng L −1 , and 23.3 ng L −1 , respectively. All of the target steroid hormones except estriol were detected in the sediment in concentrations of ND–16344 ng kg −1 . The dominant steroid hormone in the sediment of Chaohu Lake and the upstream rivers was 17α-estradiol. In the Shiwuli River and the Pai River, the dominant steroid hormones (estrone and estriol) were the same as those in the untreated municipal sewage. This confirmed the deduction that untreated municipal sewage was the major source of steroid hormone residues in these two rivers. The main steroid hormone in the water of the Hangbu River and Chaohu Lake was 17α-estradiol, the same as that in the farmland drainage. In addition, 17α-estradiol was verified as the major factor in the contribution of farmland drainage to the pollution in these rivers. The water in the Nanfei River had high concentrations of estriol and 17α-estradiol. This indicates that both untreated municipal sewage and farmland drainage were the major sources. The discharge of steroid hormones from the four rivers to Chaohu Lake was approximately 75.1 kg year −1 , with the highest contributor being 17α-estradiol (24 kg year −1 ). Therefore, based on the results of this study, the farmland drainage should be controlled to reduce the steroid hormone pollution in Chaohu Lake.

This study was designed to evaluate whether decreasing circulating progesterone (P4) or increasing circulating estradiol-17β (E2) near the time of artificial insemination (AI) in an Ovsynch protocol would increase pregnancies per AI (P/AI) in lactating dairy cows. Six hundred nineteen lactating Holstein cows (n=772 inseminations) received Ovsynch (GnRH–7 d-PGF2α–56 h-GnRH–16 h-timed AI). Cows were randomized in a 2×2 factorial experiment of 4 treatments to receive or not receive 25mg of PGF2α 24h after the standard PGF2α of Ovsynch, or 0.5mg of E2 at the time of the final GnRH of Ovsynch, or both. Blood samples were collected 24h after normal PGF2α and at final GnRH to evaluate circulating P4. Ovarian ultrasound was done at final GnRH to determine preovulatory follicle size. Ovulation was confirmed by ultrasound 5 d after AI. Treatment with additional PGF2α increased the percentage of cows that had complete luteal regression (95.6%) compared with control cows (84.6%). In contrast, additional PGF2α had no detectable effect on P/AI (control = 41.5% vs. + PGF2α=44.7%). Supplementation with E2 increased expression of estrus (84.4 vs. 37.2%), but had no effect on overall fertility and even tended to have a negative effect on fertility in cows that ovulated to the second GnRH (control = 51.5% vs. +E2=44.0%). Thus, additional treatments with PGF2α or E2 during Ovsynch can be used to increase synchronization and expression of estrus during Ovsynch, although the lack of improvement in fertility makes these treatments unwarranted.

The objectives were to determine the effects of PGF2α treatment on the prevalence of subclinical endometritis (SCE) and fertility of dairy cows. A total of 406 Holstein cows (167 primiparous and 239 multiparous) from 5 herds were used. Uterine lavage for diagnosis of SCE, PGF2α treatment, evaluation of body condition scores (BCS), and collection of blood samples for estrous cyclicity determination were performed at 21, 35, and 49 d in milk (DIM). Polymorphonuclear cells (PMN) were quantified and thresholds for diagnosing SCE were selected by receiver operating characteristics analysis. Cows classified as having SCE at 35 DIM (≥6.5% PMN) and 49 DIM (≥4.0% PMN) had increased time to pregnancy; however, cows classified as having SCE at 21 DIM (≥8.5% PMN) did not. Median days to pregnancy were delayed by 30 (151 vs. 121 d) and 40 (169 vs. 129) d for cows classified as having SCE at 35 and 49 DIM, respectively. Treatment with PGF2α did not affect the prevalence of SCE either at 35 (37.9 vs. 38.4%) or at 49 DIM (34.0 vs. 40.4%). Treatment with PGF2α did not affect time to first insemination (AI; median 76 DIM for cows treated with PGF2α; 79 DIM for control. Nonetheless, PGF2α treatment increased pregnancy to first AI in all the cows (35.5 vs. 24.1%) and hazard ratio (HR) of pregnancy in cows with BCS ≤2.5 when all of the cows were evaluated (HR = 1.5; 95% confidence interval; CI = 1.1 to 2.0) and when only cows without SCE were evaluated (HR = 1.8; 95% CI = 1.2 to 2.7). Treatment with PGF2α did not affect the hazard of pregnancy in cows with SCE at 49 DIM (HR = 0.9; 95% CI = 0.6 to 1.3). In these farms, treatment with PGF2α did not affect SCE or time to first insemination, but did increase first-service pregnancy per AI and decreased time to pregnancy in cows with low BCS.

The aim of this study was to determine whether an increase in circulating estrogen concentrations would increase percentage pregnant per artificial insemination (PP/AI) in a timed AI protocol in high-producing lactating dairy cows. We analyzed only cows having a synchronized ovulation to the last GnRH of the Ovsynch protocol (867/1,084). The control group (n = 420) received Ovsynch (GnRH – 7 d – PGF2α – 56h – GnRH – 16h – timed AI). The treatment group (n = 447) had the same timed AI protocol with the addition of 1mg of estradiol-17β (E2) at 8h before the second GnRH injection. Ovarian ultrasound and blood samples were taken just before E2 treatment of both groups. In a subset of cows (n = 563), pressure-activated estrus detection devices were used to assess expression of estrus at 48 to 72h after PGF2α treatment. Ovulation was confirmed by ultrasound 7 d after timed AI. Treatment with E2 increased expression of estrus but overall PP/AI did not differ between E2 and control cows. There was an interaction between treatment and expression of estrus such that PP/AI was greater in E2-treated cows that showed estrus than in E2-treated or control cows that did not show estrus and tended to be greater than control cows that showed estrus. There was evidence for a treatment by ovulatory follicle size interaction on PP/AI. Supplementation with E2 improved PP/AI in cows ovulating medium (15 to 19mm) but not smaller or larger follicles. The E2 treatment also tended to improve PP/AI in primiparous cows with low (≤2.5) body condition score, and in cows at first postpartum service compared with Ovsynch alone. In conclusion, any improvements in PP/AI because of E2 treatment during a timed AI protocol appear to depend on expression of estrus, parity, body condition score, and size of ovulatory follicle.

OBJECTIVE: New-onset diabetes after kidney transplantation (NODAT) has adverse clinical and economic implications. A risk score for NODAT could help identify research subjects for intervention studies. RESEARCH DESIGN AND METHODS: We conducted a single-center retrospective cohort study using pretransplant clinical and laboratory measurements to construct a risk score for NODAT. NODAT was defined by hemoglobin A1c (HbA1c) ≥6.5%, fasting serum glucose ≥126 mg/dL, or prescribed therapy for diabetes within 1 year posttransplant. Three multivariate logistic regression models were constructed: 1) standard model, with both continuous and discrete variables; 2) dichotomous model, with continuous variables dichotomized at clinically relevant cut points; and 3) summary score defined as the sum of the points accrued using the terms from the dichotomous model. RESULTS: A total of 316 subjects had seven pretransplant variables with P < 0.10 in univariate logistic regression analyses (age, planned corticosteroid therapy posttransplant, prescription for gout medicine, BMI, fasting glucose and triglycerides, and family history of type 2 diabetes) that were selected for multivariate models. Areas under receiver operating curves for all three models were similar (0.72, 0.71, and 0.70). A simple risk score calculated as the sum of points from the seven variables performed as well as the other two models in identifying risk of NODAT. CONCLUSIONS: A risk score computed from seven simple pretransplant variables can identify risk of NODAT.

The objectives of this study were to evaluate the effects of method of presynchronization and source of supplemental Se on uterine health and reproductive performance of lactating dairy cows. Holstein cows (n=512) were assigned randomly to 2 methods of presynchronization, Presynch (2 PGF2a given 14 d apart) or CIDR-PS (controlled internal drug releasing inserted for 7 d with an injection of PGF2a at removal) and 2 sources of Se, sodium selenite (SS) or selenized yeast (SY) supplemented at 0.3 mg/kg from 25 d before calving to 80 d in milk (DIM) arranged in a 2×2 factorial. Cows were inseminated following the Ovsynch protocol (d 0 GnRH, d 7 PGF2a, d 9 GnRH, timed artificial insemination (AI) 12h after the final GnRH) starting at 12 and 3 d after Presynch and CIDR-PS, respectively. Cows were diagnosed for pregnancy at 28, 42, and 56 d after AI. Source of Se did not influence uterine health and resumption of cyclicity, but fewer CIDR-PS than Presynch cows were cyclic at the beginning of the Ovsynch, although differences in the proportion cyclic may have been caused by the timing when corpus luteum evaluations were performed in the different pre-synchronization treatments. Ovulatory responses were not influenced by source of Se. However, the CIDR-PS increased ovulation to the first GnRH, double ovulation to the final GnRH, and size of ovulatory follicle at PGF2a and final GnRH of the Ovsynch, but did not influence ovulation at the final GnRH of the Ovsynch. Concentrations of estradiol during the Ovsynch increased with follicle diameter and were greater for cows receiving CIDR-PS than Presynch, but they were not influenced by source of Se. Pregnancy per AI on d 28 (32.7%), 42 (28.5%), and 56 (25.9%) after AI, and pregnancy loss (20.5%) from 28 to 56 d were not influenced by source of Se or method of presynchronization. Although cows receiving CIDR-PS had an increased incidence of ovulation to the first GnRH (73.2 vs. 57.8%) and double ovulation to the final GnRH of the Ovsynch (18.7 vs. 9.0%), both of which enhanced pregnancy, the CIDR-PS protocol did not improve pregnancy per AI or reduce pregnancy loss compared with presynchronization with PGF2a alone.

Testosterone is integral to men’s sexual and overall health, but there is a gradual decline in the ageing male. The topical administration of testosterone is a valuable option as a supplement (replacement) therapy to alleviate hypogonadal symptoms. The clinical efficacy of a compounded testosterone 5% topical gel was assessed retrospectively in a male patient in his seventies by evaluating the laboratory testing of the serum total testosterone and the results of a validated androgen deficiency questionnaire. After treatment, the patient’s hypogonadal symptoms improved and the serum total testosterone level achieved was considered clinically optimal. The skin permeation of the testosterone topical gel (biological testing) was evaluated in vitro using the Franz finite dose model and human cadaver skin, and it is shown that testosterone can penetrate into and through ex vivo human skin. Testosterone therapy is often prescribed for extended periods, and consequently, it is crucial to determine the beyond-use date of the compounded formulations. The analytical testing involved a valid, stability-indicating assay method for compounded testosterone 0.5% and 20% topical gels. This multidisciplinary study shows evidence supporting topically applied testosterone’s clinical efficacy and the compounded formulations’ extended stability. Personalized, topical testosterone therapy is a promising alternative in current therapeutics for hypogonadal patients.

Objective: The aim of this study was to investigate the association between maternal overweight before pregnancy and offspring asthma in an ongoing birth cohort study. Maternal overweight may affect the pulmonary and immunological development of the fetus in utero because of the increased levels of inflammatory factors associated with being overweight and thereby increase the asthma risk in childhood. Design: Birth cohort study with follow-up until 8 years of age. Subjects: The study population included 3963 children and their mothers who participated in the Prevention and Incidence of Asthma and Mite Allergy study. Measurements: Maternal overweight before pregnancy was defined as a body mass index (BMI) above 25 kg m−2. Data on wheeze, dyspnea and prescription of inhaled corticosteroids of the child were reported yearly by the parents in a questionnaire. Sensitization to inhalant allergens and bronchial hyperresponsiveness (BHR) were determined at 8 years. Effect modification by predisposition for asthma in the child was tested. Data were analyzed by logistic regression and generalized estimating equations analyses. Results: At 8 years, 14.4% (n=571) of the children had asthma. In total, 20.9% (n=830) of the mothers were overweight before pregnancy. In children predisposed for asthma (n=1058), maternal overweight before pregnancy was associated with an increased risk of asthma in the child at 8 years (OR=1.52, 95% CI: 1.05–2.18) after adjustment for confounding factors, birth weight and the child's BMI. No association was observed in children without a predisposition (OR=0.86, 95% CI: 0.60–1.23). There was no association with sensitization or BHR. Conclusion: Children with a predisposition for asthma may have a higher risk to develop asthma during childhood when their mothers are overweight before pregnancy, irrespective of the child's BMI.

The objectives were to evaluate the effect of supplemental progesterone during a timed artificial insemination (TAI) protocol on pregnancy per insemination and pregnancy loss. Lactating dairy cows from 2 dairy herds were presynchronized with 2 injections of PGF2α 14 d apart, and cows observed in estrus following the second PGF2α injection were inseminated (n=1,301). Cows not inseminated by 11 d after the end of the presynchronization were submitted to the TAI protocol (d 0 GnRH, d 7 PGF2α, d 8 estradiol cypionate, and d 10 TAI). On the day of the GnRH of the TAI protocol (study d 0), cows were assigned randomly to receive no exogenous progesterone (control=432), one controlled internal drug-release (CIDR) insert (CIDR1=440), or 2 CIDR inserts (CIDR2=440) containing 1.38g of progesterone each from study d 0 to 7. Blood was sampled on study d 0 before insertion of CIDR for determination of progesterone concentration in plasma, and cows with concentration <1.0ng/mL were classified as low progesterone (LP) and those with concentration ≥1.0ng/mL were classified as high progesterone (HP). From a subgroup of 240 cows, blood was sampled on study d 3, 7, 17 and 24 and ovaries were examined by ultrasonography on study d 0 and 7. Pregnancy was diagnosed at 38±3 and 66±3 d after AI. Data were analyzed including only cows randomly assigned to treatments and excluding cows that were inseminated after the second PGF2α injection. The proportion of cows classified as HP at the beginning of the TAI protocol was similar among treatments, but differed between herds. Concentrations of progesterone in plasma during the TAI protocol increased linearly with number of CIDR used, and the increment was 0.9ng/mL per CIDR. The proportion of cows with plasma progesterone ≥1.0ng/mL on study d 17 was not affected by treatment, but a greater proportion of control than CIDR-treated cows had asynchronous estrous cycles following the TAI protocol. Treatment with CIDR inserts, however, did not affect pregnancy at 38±3 and 66±3 d after AI or pregnancy loss.