Creating models for the prediction of colostrum quantity, quality, and immunoglobulin G yield in multiparous Jersey cows from performance in the previous lactation and environmental changes.

With multiparous Jersey cows, colostrum production seems to be variable. Due to this, we aimed to identify specific variables involved in colostrum production and quality. From 2021 to 2023, data from 28 US farms (415 multiparous Jersey cows) were used to investigate if colostrum yield, IgG concentration (g/L), and IgG yield (g) could be predicted by farm variables and transmitting abilities. With the data collected, multiple regression equations were developed to aid in predicting colostrum yield, IgG concentration, and IgG yield. Colostrum was weighed and sampled for IgG analysis. Dairy Herd Information (DHI), calving, diet, and management information data were compiled. Days below 5°C (D<), days above 23°C (D>), and days between 5 and 23°C (D) were recorded. We evaluated transmitting abilities for milk, fat, protein, and dollars; previous lactation milk yield, fat percent, fat yield, protein percent, protein yield, previous lactation somatic cell score, previous lactation days open, previous lactation days dry, previous lactation days in milk, and previous parity; and current lactation parity, days dry, and calving information, birth ordinal day, and latitude. Colostrum yield, IgG yield, and concentration had 1 added to correct for values = 0. After addition, values >0 were transformed to ln or log10. Nontransformed variables were also used to develop the model. Variance inflation factor analysis was conducted, followed by backward elimination. The log10 colostrum yield model (R2 = 0.55; ß in parentheses) included herd size (-0.0001), ordinal days (-0.001), ln ordinal days (0.07), latitude (-0.02), dry period length (0.004), D< (-0.005), D (-0.003), time to harvest (0.05), ln time to harvest (-0.35), IgG (-0.004), log10 IgG (0.46), feedings per day (0.06), ln pasture access (-0.13), and ln previous lactation days open (0.14). The model showed that previous lactation days open contributed the most toward increasing and latitude contributed the most toward decreasing colostrum yield. The IgG model (R2 = 0.21) included herd size (0.02), D> (0.38), ln time to harvest (-19.42), colostrum yield (-4.29), ln diet type (18.00), ln previous lactation fat percent (74.43), and previous parity (5.72). The model showed that previous lactation milkfat percent contributed the most toward increasing and time from parturition to colostrum harvest contributed the most toward decreasing colostrum IgG concentration. The log10 IgG yield model (R2 = 0.79) included ln ordinal days (0.03), time to harvest (-0.01), colostrum yield (-0.11), ln colostrum yield (1.20), ln pasture access (-0.09), ln previous lactation fat percent (0.53), and previous parity (0.02). The model showed that colostrum yield contributed the most toward increasing IgG yield, followed by previous lactation milkfat percentage. Pasture access contributed the most toward decreasing IgG yield, although the contribution was very small. These models were validated using 39 samples from 22 farms. Actual minus predicted colostrum yield and IgG concentration and yield were 0.89 kg, -21.10 g/L, and -65.15 g, respectively. These models indicate that dry period management and cow information can predict colostrum yield and IgG concentration and yield.

Supplementing sodium butyrate to limit-fed heifers: Effects on growth, coccidiosis, urinary purine derivatives, and apparent total-tract nutrient digestibility.

The objective of this study was to assess the growth, apparent total-tract digestibility of nutrients, the prevalence of coccidia, and purine derivatives in postweaning heifers when limit-fed a diet supplemented with sodium butyrate (SB). A 12 wk randomized complete block experiment was conducted using 24 Holstein heifers (92.8 d ± 1.9 d of age and initial body weight [BW] of 99.6 ± 15.2 kg [mean ± standard deviation]). Treatments were 100 g soybean meal (control; CON) and 0.75 g of SB/kg of BW + 100 g soybean meal (SB). Diets were formulated to contain 16.4% crude protein, 2.27 Mcal/kg metabolizable energy (ME), and fed at a feed out rate of 2.15% of BW on a dry matter basis. Intakes were recorded daily while growth measurements and BW were recorded weekly. Urine and fecal samples were taken every 2 wk. On d 42 through d 49 an apparent total-tract digestibility phase took place using acid detergent insoluble ash as a marker. Growth measurements were similar among treatments except CON heifers grew longer and tended to be taller at the withers. A trend was observed for CON animals to have lower levels of coccidian oocytes by week. Heifers fed SB had lower blood glucose levels and higher levels of ketones in their blood. Urinary volume was greater for heifers fed SB throughout the 12 wk study. Total purine derivatives were greater in CON heifers. Dry matter, organic matter and acid detergent fiber digestibilities were greater for heifers fed SB compared with CON heifers. Crude protein, neutral detergent fiber, and ash digestibilities tended to be greater in heifers fed SB than in CON heifers. These results suggested no growth benefit of supplementing SB to limit-fed heifers; however, apparent total-tract fiber, ash, and crude protein digestibilities were improved in the SB fed heifers likely due to improved ruminal and intestinal development.

The effect of meloxicam on neonatal dairy calves: Immunoglobulin G uptake and preweaning performance.

Objectives of this study were to determine effects of meloxicam administered in 2 forms on IgG uptake, growth, and health of preweaned calves. Sixteen Holstein bulls and 14 heifers with a body weight (BW) of 44.3 ± 5.24 kg were blocked by birth date in a randomized complete block design. Calves were removed from the dam before suckling, weighed, and randomly assigned to 1 of 3 treatments: (1) colostrum replacer (CR) at 0 h with no meloxicam (control; CON), (2) 1 mg/kg of BW of meloxicam in pill form before CR (PL), or (3) 1 mg/kg of BW of meloxicam mixed in solution with CR (SL). Calves were fed 675 g of dry matter of CR, providing a volume of 3 L and 180 g of IgG. Blood samples were collected at 0 h to analyze initial IgG and ketone concentrations, and at 6, 12, 18, and 24 h to analyze IgG uptake. At 24 h, calves were fed 432 g of dry matter of 24% crude protein milk replacer (MR) split in 2 feedings, and free choice starter and water until 42 d. Weekly blood samples were analyzed for glucose, plasma urea nitrogen, and ketone concentrations. Time of consumption of MR, BW, length, hip and withers height, and heart girth were recorded weekly. All calves achieved adequate transfer of immunity. Meloxicam did not affect apparent efficiency of absorption, serum total protein, or IgG uptake at 6, 18, and 24 h; however, meloxicam-treated calves had lesser IgG concentrations at 12 h (24.40 and 22.59 g/L for PL and SL, respectively) compared with CON (28.47 g/L). Meloxicam treatment did not affect BW. Calves that received PL tended to gain length at a faster rate (0.24 cm/d) than those that received SL (0.19 cm/d). Meloxicam treatment did not affect MR intake, time of consumption of MR, total dry matter intake, or feed efficiency. Meloxicam-treated calves tended to consume more starter (560.4 and 515.4 g/d for PL and SL, respectively) than those that received CON (452.6 g/d). Ketone levels tended to be greater in meloxicam-treated calves (0.15 and 0.17 mmol/L for PL and SL, respectively), suggesting improved rumen development compared with those that received CON (0.12 mmol/L). Meloxicam treatment did not affect plasma urea nitrogen . Glucose concentrations of calves that received PL (73.2 mg/dL) were less than those that received SL (83.3 mg/dL). Results of this study suggest that meloxicam given at 0 h offers positive effects on starter intake, and possibly rumen development, of preweaned dairy calves. Treatment PL, as compared with SL, offered positive results for rumen development, indicated by lower blood glucose levels.

Sodium butyrate and monensin supplementation to postweaning heifer diets: Effects on growth performance, nutrient digestibility, and health.

The objective of this study was to evaluate growth and performance of postweaning heifers supplemented with monensin (MON), sodium butyrate (SB), or the combination of MON and SB (MSB) compared with heifers not receiving these feed additives. Forty Holstein heifers [mean age 84.2 ± 1.2 d; body weight (BW) 99.8 ± 10.8 kg (mean ± SD)] were housed in a freestall barn, blocked by birth date, and randomly assigned to 1 of 4 treatments in a randomized complete block design. Treatments were (1) 100 g of soybean meal carrier (control; CON); (2) 0.75 g of SB/kg of BW + carrier (SB); (3) 1 mg of MON/kg of BW + carrier (MON); (4) 1 mg of MON/kg of BW + 0.75 g of SB/kg of BW (MSB). Data were analyzed using single degree of freedom contrasts evaluating CON versus additives (ADD), SB versus MON, and SB and MON versus MSB. Treatments were hand-mixed daily. Feed and orts were measured daily and frozen at -20°C. Orts samples were subsampled for dry matter (DM) determination, and total mixed ration samples were taken weekly and composited monthly for DM and nutrient analysis. Initial BW, heart and paunch girths, body length, blood samples, and fecal coccidia counts were measured before the start and weekly during the 12-wk trial. Blood samples were analyzed for glucose, plasma urea nitrogen (PUN), and ketone concentrations. Apparent total-tract nutrient digestibility was determined from d 21 to 27 and from d 63 to 69 using acid detergent insoluble ash as a marker. Daily dry matter intake (DMI) and metabolizable energy intake were increased in ADD compared with CON, and average BW, final BW, and heart girth tended to increase. Whereas MSB tended to be greater than SB and MON for heart girth, feed efficiency was greater with MON compared with SB. Compared with CON, ADD decreased coccidia counts. No effect of treatment on PUN was detected. Monensin and SB tended to have greater plasma glucose than MSB did. Average blood ketone concentrations were greater with ADD versus CON, in SB versus MON, and in MSB versus SB and MON. During the wk-3 digestibility phase, DMI tended to be greater in heifers fed SB versus MON, as well as in heifers fed MSB versus SB and MON. Digestibility of nutrients were similar, except that starch digestibility was increased in heifers fed MSB versus SB and MON. During the wk-9 digestibility phase, DMI and digestibility of nutrients were similar, except NDF, which tended to be greater in CON than in ADD. Overall, ADD resulted in positive growth and reduced coccidia compared with CON.

Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial.

The effects of higher than recommended vitamin D doses on bone mineral density (BMD) and quality are not known. In this study, higher intakes, in postmenopausal women undergoing weight control over 1 year, had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry. INTRODUCTION: Studies examining how bone responds to a standard dose of vitamin D supplementation have been inconsistent. In addition, the effects of higher doses on BMD and quality are not known. Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance. METHODS: This 1-year-long, randomized, double-blind controlled study addresses whether vitamin D supplementation, in healthy overweight/obese older women, affects BMD and bone structural parameters. In addition, bone turnover and serum total, free, and bioavailable 25-hydroxyvitamin D (25OHD) responses to one of three daily levels of vitamin D3 (600, 2000, 4000 IU) with 1.2 Ca g/day during weight control were examined. RESULTS: Fifty-eight women (age, 58 ± 6 years; body mass index, 30.2 ± 3.8 kg/m2, serum 25OHD, 27.3 ± 4.4 ng/mL) were randomized to treatment. After 1 year, serum 25OHD concentrations increased to 26.5 ± 4.4, 35.9 ± 4.5, and 41.5 ± 6.9 ng/mL, in groups 600, 2000, and 4000 IU, respectively, and differed between groups (p < 0.01). Weight change was similar between groups (-3.0 ± 4.1 %). Cortical (Ct) thickness of the tibia changed by -1.5 ± 5.1 %, +0.6 ± 3.2 %, and +2.0 ± 4.5 % in groups 600, 2000, and 4000 IU, respectively, and each group was significantly different from each other (p < 0.05). CONCLUSION: The decline in Ct thickness was prevented with higher vitamin D3 supplementation, but there were no other significant changes due to treatment over 1 year. Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies.

The associations of indoor environment and psychosocial factors on the subjective evaluation of Indoor Air Quality among lower secondary school students: a multilevel analysis.

Subjective evaluation of Indoor Air Quality (subjective IAQ) reflects both building-related and psychosocial factors, but their associations have rarely been studied other than on the individual level in occupational settings and their interactions have not been assessed. Therefore, we studied whether schools' observed indoor air problems and psychosocial factors are associated with subjective IAQ and their potential interactions. The analysis was performed with a nationwide sample (N = 195 schools/26946 students) using multilevel modeling. Two datasets were merged: (i) survey data from students, including information on schools' psychosocial environment and subjective IAQ, and (ii) data from school principals, including information on observed indoor air problems. On the student level, school-related stress, poor teacher-student relationship, and whether the student did not easily receive help from school personnel, were significantly associated with poor subjective IAQ. On the school level, observed indoor air problem (standardized ß = -0.43) and poor teacher-student relationship (standardized ß = -0.22) were significant predictors of poor subjective IAQ. In addition, school-related stress was associated with poor subjective IAQ, but only in schools without observed indoor air problem (standardized ß = -0.44).

[Treatment side effects and follow-up of malignant melanoma]. / Therapienebenwirkungen und Nachsorge bei malignem Melanom.

Side effects in the therapy of malignant melanoma are primarily of importance for radiologists in advanced tumor stages. The available treatment options and their respective side effect profiles have undergone a profound change in recent years after the introduction of modern oncological therapies (e.g. immunotherapy and targeted therapy) with an increasing focus on individual tumor biology and differ significantly from those of classical chemotherapy. The immunotherapeutic agents, in particular ipilimumab, take on a special position because of their specific immune-mediated mechanisms of action and the associated side effects, so-called immune-related adverse events (irAE). The majority of the treatment effects are manifested on the skin (> 50 %) and are generally not detectable by diagnostic radiology. Only a comparatively small proportion of treatment side effects is detectable with diagnostic imaging (15-20 %) but as in the example of therapy-induced colitis with ipilimumab, may be rapidly fatal. In addition to colitis (10-20 %) further therapy side effects apparent in diagnostic imaging are hypophysitis (1.8-17 %), thyroiditis (0.8 %), myositis (1.7 %), fasciitis and sarcoid-like lymph node alterations (6.8 %). To detect radiologically detectable side effects early on and to delineate them especially from tumor progression and (opportunistic) infections, detailed knowledge of the therapeutic methods for melanoma, the mechanisms of action and in particular the sometimes very specific side effects is imperative for radiologists.

The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer.

BACKGROUND: The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in urinary bladder cancer and its possibilities as a therapeutic target. METHODS: Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA. RESULTS: In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA. CONCLUSIONS: STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer.

Transanal endoscopic microsurgery for rectal carcinoids: the largest reported United States experience.

AIM: Rectal carcinoids are often inadequately resected by snare excision during colonoscopy. Transanal endoscopic microsurgery is a minimally invasive procedure with low morbidity that offers full-thickness excision with a low rate of negative margins. It presents an excellent alternative to radical surgery for mid and proximally located lesions. We report the largest United States (US) experience in the use of transanal endoscopic microsurgery for rectal carcinoids. METHOD: Data of patients who had undergone transanal endoscopic microsurgery for rectal carcinoids were prospectively collected and retrospectively analyzed. Patient and tumour characteristics, operative and perioperative details, as well as oncological outcomes were reviewed. RESULTS: Over a 12-year period, 24 patients underwent transanal endoscopic microsurgery for rectal carcinoids. Of these, six (25%) were primary surgical resections and 18 (75%) were performed after incomplete snare excisions during colonoscopy. Three (17%) patients who underwent full-thickness resection after snare excision had residual tumour on histopathological examination. Negative margins were obtained in all cases. No recurrences were noted. CONCLUSION: Transanal endoscopic microsurgery is effective and safe for the surgical resection of rectal carcinoids<2 cm in diameter, with typical features and located more than 5 cm from the anal verge. Transanal endoscopic microsurgery can be used for primary resection or for resection after incomplete colonoscopic snare excision.

Perfluorooctanoic acid and perfluorooctane sulfonate in liver and muscle tissue from wild boar in Hesse, Germany.

Approximately 15,000 tons of wild boar meats (Sus scrofa) are consumed per year in Germany. Boar meat therefore plays a definite role in regard to human diet. Because they are omnivores and because of their high body fat quotient, wild boar may accumulate large concentrations of persistent organic compounds, such as halogenated hydrocarbons, and could thus possibly serve as bioindicators for persistent xenobiotics. In addition, consumption of wild boar meat and liver could lead to increased contaminant levels in humans. Between 2007 and 2009, we tested a total of 529 livers and 506 muscle tissue samples from wild boar for the presence of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). PFOA concentrations ≤45 µg/kg and PFOS concentrations ≤1,780 µg/kg were detected in the liver samples. PFOA concentrations ≤7.4 µg/kg and PFOS concentrations ≤28.6 µg/kg were detected in muscle tissue. Our results show that PFOS may be detected in considerably greater concentrations than PFOA in organs and tissues, which is in agreement with results from other published studies. The comparisons between both organs for the same substance, as well as the comparisons between the substances within an organ, showed clear and statistically significant differences at P < 0.0001. Assuming a tolerable daily intake value of PFOA (1.5 µg/kg bw/d) and PFOS (0.15 µg/kg bw/d) as recommended by the European Food Safety Authority, the results of model calculations based on the maximum concentrations of PFOA and PFOS found in wild boar indicate that there should be no PFC-related health danger resulting from moderate consumption of wild boar meat or liver.

Obesity alters cortical and trabecular bone density and geometry in women.

UNLABELLED: The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone using quantitative computed tomography. A higher body mass index (BMI) was positively associated with trabecular and cortical bone parameters, and serum parathyroid hormone, and negatively associated with cortical volumetric bone mineral density (vBMD) and serum 25-hydroxy-vitamin D. When BMI is greater than 35 kg/m(2), adiposity affects vBMD and may explain the higher fracture risk in this population without low BMD. INTRODUCTION: The influence of adult obesity on the trabecular and cortical bone, geometry, and strength has not been fully addressed. The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone mass and geometry, over a wide range of body weights. METHODS: We examined 211 women (25-71 years; BMI 18-57 kg/m(2)) who were classified into three categories of BMI (kg/m(2)) including normal-weight (BMI<25), overweight and obese-class I (BMI 25-35) and obese-class II-III (BMI>35), and also by menopausal status. Volumetric bone mineral density (mg/cm(3)), trabecular, and cortical components as well as geometric characteristics at the 4%, 38%, and 66% from the distal tibia were measured by peripheral quantitative computed tomography, and serum was analyzed for parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25OHD). RESULTS: Higher BMI was associated with greater values of trabecular bone and cortical BMC and area and PTH (r>0.39, p<0.001), but lower cortical vBMD and 25OHD (r>-0.27, p<0.001). When controlling for lower leg muscle area, fat area was inversely associated with cortical vBMD (r=-0.16, p<0.05). Premenopausal obese women with both higher BMI and PTH had lower cortical vBMD (r<-0.40, p<0.001). While age is a predictor for most bone variables, fat mass explains more variance for vBMD, and lean mass and 25OHD explain greater variance in geometric and strength indices (p<0.05). CONCLUSIONS: Severe obesity (BMI>35) increases trabecular vBMD and in the presence of a higher PTH is associated with a lower cortical vBMD without compromising bone geometry and strength. Whether or not a lower cortical vBMD in obesity influences fracture risk over time needs to be further explored.

Carryover of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from soil to plants.

Within the scope of a joint project to study soil-to-plant carryover of polyfluorinated compounds (PFCs), five cultivated plants (spring wheat, oats, potatoes, maize, and perennial ryegrass) were sown or planted in Mitscherlich pots. Six variants per species were used, each with a different concentration level of PFOA and PFOS (from 0.25 to 50 mg/kg as aqueous solution) to detect possible concentration dependence in the transfer of these two PFCs from soil to plant. PFOA and PFOS were detected by liquid chromatography-tandem mass spectrometry after appropriate sample preparation (partial drying, mincing, homogenizing, extraction). Since PFOA and PFOS presently represent the most widely studied PFCs, they are classified as "leading compounds." The results show that concentrations of PFOA/PFOS in the plants vary greatly, depending on the concentrations applied to the soil. PFOA values were higher than PFOS values in all plants except potatoes, in which these differences could be quite substantial. From the results presented here it can be seen that uptake and storage are much more intensive in the vegetative portion of the plant than relocation in the storage organs. This is particularly evident from the the comparison of concentrations found in the grain and ear and those in the straw or rest of the plant in spring wheat, oats, and maize. Transfer from "soil to crops" provides a possible explanation for the presence of PFCs in foodstuffs and in human body fluids such as blood, plasma, serum, or breast milk. The aim of the present study was to determine whether a statistically significant, concentration-dependent carryover of PFOA and PFOS in crop plants can take place, which would provide a potential entrance point for these substances into the food chain.

Molecular genetics of bladder cancer: an update.

Urinary bladder cancer is a heterogeneous disease with tumors ranging from papillary non-invasive to solid muscle infiltrating high grade tumors. There are mainly three problems after initial management: recurrence, progression to higher stage and metastases. The respective risk is well known for each of the stages of the disease but not sufficiently for individual optimal risk assessments. The clinical need is initially to establish the correct risk irrespective of later treatment that is to find prognostic factors. Secondarily it is important to develop predictive factors for each specific therapy. With the advent of array-based molecular profiling it is possible to obtain a more complete picture of the cancer biology and thus hope to improve the prediction of risk. Today the microarray approach is implemented at DNA, RNA and protein level. Reported chromosomal alterations in low-grade papillary tumors are few and the most common are 9q and 9p deletions. Activation of the MAPK pathway through mutations of FGFR3, RAS or PI3K seems to be crucial in the genesis of these low malignant tumors. Muscle infiltrating bladder tumors typically have more genetic aberrations than non-muscle invasive cancers. Key genes are related to the p53 and RB pathways. Gene-expression signatures correlated to stage, CIS, progression and recurrence have been proposed but require further validation.

Identification of novel deletion breakpoints bordered by segmental duplications in the NF1 locus using high resolution array-CGH.

BACKGROUND: Segmental duplications flanking the neurofibromatosis type 1 (NF1) gene locus on 17q11 mediate most gene deletions in NF1 patients. However, the large size of the gene and the complexity of the locus architecture pose difficulties in deletion analysis. We report the construction and application of the first NF1 locus specific microarray, covering 2.24 Mb of 17q11, using a non-redundant approach for array design. The average resolution of analysis for the array is approximately 12 kb per measurement point with an increased average resolution of 6.4 kb for the NF1 gene. METHODS: We performed a comprehensive array-CGH analysis of 161 NF1 derived samples and identified heterozygous deletions of various sizes in 39 cases. The typical deletion was identified in 26 cases, whereas 13 samples showed atypical deletion profiles. RESULTS: The size of the atypical deletions, contained within the segment covered by the array, ranged from 6 kb to 1.6 Mb and their breakpoints could be accurately determined. Moreover, 10 atypical deletions were observed to share a common breakpoint either on the proximal or distal end of the deletion. The deletions identified by array-CGH were independently confirmed using multiplex ligation-dependent probe amplification. Bioinformatic analysis of the entire locus identified 33 segmental duplications. CONCLUSIONS: We show that at least one of these segmental duplications, which borders the proximal breakpoint located within the NF1 intron 1 in five atypical deletions, might represent a novel hot spot for deletions. Our array constitutes a novel and reliable tool offering significantly improved diagnostics for this common disorder.

Late Quaternary faulting in the Sevier Desert driven by magmatism.

Seismic hazard in continental rifts varies as a function of strain accommodation by tectonic or magmatic processes. The nature of faulting in the Sevier Desert, located in eastern Basin and Range of central Utah, and how this faulting relates to the Sevier Desert Detachment low-angle normal fault, have been debated for nearly four decades. Here, we show that the geodetic signal of extension across the eastern Sevier Desert is best explained by magma-assisted rifting associated with Plio-Pleistocene volcanism. GPS velocities from 14 continuous sites across the region are best-fit by interseismic strain accumulation on the southern Wasatch Fault at c. 3.4 mm yr-1 with a c. 0.5 mm yr-1 tensile dislocation opening in the eastern Sevier Desert. The characteristics of surface deformation from field surveys are consistent with dike-induced faulting and not with faults soling into an active detachment. Geologic extension rates of c. 0.6 mm yr-1 over the last c. 50 kyr in the eastern Sevier Desert are consistent with the rates estimated from the geodetic model. Together, these findings suggest that Plio-Pleistocene extension is not likely to have been accommodated by low-angle normal faulting on the Sevier Desert Detachment and is instead accomplished by strain localization in a zone of narrow, magma-assisted rifting.

Bone turnover and density in obese premenopausal women during moderate weight loss and calcium supplementation.

Bone turnover is increased during weight loss in postmenopausal women and can be suppressed with calcium supplementation. In this study, we assessed the influence of energy restriction with and without calcium supplementation (1 g/day) in premenopausal women. Thirty-eight obese premenopausal women (body mass index [BMI] of 35.0 +/- 3.9 kg/m2) completed a 6-month study of either moderate weight loss or weight maintenance. During weight loss, women were randomly assigned to either a calcium supplementation (n = 14) or placebo group (n = 14) and lost 7.5 +/- 2.5% of their body weight. The control group of women (n = 10) maintained their body weight. Total body and lumbar bone mineral density (LBMD) and content were measured by dual-energy X-ray absorptiometry (DXA) at baseline and after weight loss. Throughout the study, blood and urine samples were collected to measure bone turnover markers and hormones. During moderate energy restriction, dietary calcium intake decreased (p < 0.05) and the bone resorption marker deoxypyridinoline (DPD) increased slightly (p < or = 0.05) without evidence of bone loss. Calcium supplementation during weight loss tended to increase lumbar BMD by 1.7% (p = 0.05) compared with the placebo or weight maintenance groups. In contrast to our previous findings in postmenopausal women, premenopausal obese women who consume a low calcium diet do not lose bone over a 6-month period, whether their weight is stable or decreasing moderately.

Calcium supplementation suppresses bone turnover during weight reduction in postmenopausal women.

Bone mobilization, lowering of bone mineral density (BMD), and osteoporotic fractures are recognized in postmenopausal women with weight loss. Because a high-calcium intake suppresses bone loss in peri- and postmenopausal women, the present randomized, double-blind, placebo-controlled study was designed to test the hypothesis that calcium supplementation prevents net bone mobilization and consequent bone mineral loss during voluntary weight reduction in obese postmenopausal women. Subjects were placed on a moderate energy-restricted diet and either calcium supplementation (1 g/day) or placebo for 6 months. Body weight, bone turnover markers (pyridinium cross-links), osteocalcin, and parathyroid hormone (PTH) were measured at treatment weeks 1-5, 7, 10, 13, 16, 20, and 25. Total body BMD, insulin-like growth factor, 25-hydroxyvitamin D, and sex hormone binding globulin (SHBG) were measured at baseline and week 25. The calcium supplemented (n = 15; age 60.9 +/- 9.4 years, body mass index [BMI] 33.2 +/- 4.6 kg/m2) and placebo (n = 16; age 55.8 +/- 8.3 years, BMI 32.9 +/- 4.5 kg/m2) groups lost similar amounts of weight over the study interval (10.2 +/- 5.3% vs. 10.0 +/- 5.2%) and both groups increased SHBG (p < 0.001). There was a statistical effect of calcium supplementation during weight loss to suppress pyridinium cross-links, osteocalcin, and PTH (p < 0.05, < 0.01, and < 0.05, respectively). Loss of BMD tended to be greater in the placebo group by 1.4% (p < 0.08) after weight loss. One gram per day calcium supplementation normalizes the increased calcium-PTH axis activity and the elevated bone turnover rate observed during moderate voluntary energy restriction in postmenopausal women.

Moderate energy restriction increases bone resorption in obese postmenopausal women.

BACKGROUND: Weight reduction reduces bone mineral density (BMD) and increases the risk of osteoporosis. OBJECTIVE: We investigated whether bone is mobilized in postmenopausal women during energy restriction and whether hormones regulate bone turnover and mass. DESIGN: Twenty-seven obese postmenopausal women with a mean (+/-SD) age of 55.9 +/- 7.9 y and body mass index (in kg/m(2)) of 33.0 +/- 3.8 completed the 6-mo study. Fourteen women followed a moderate energy-restricted diet (WL group) and 13 control subjects maintained their body weight (WM group). Body weight, bone turnover markers, serum parathyroid hormone (PTH), and dietary intake were measured throughout the study. Total-body BMD, sex hormone binding globulin, leptin, and estrone were measured at baseline and at week 25. RESULTS: In the WL group, body weight decreased by 10.2 +/- 5.5% (P < 0.001), body fat mass decreased by 18.7 +/- 11.3% (P < 0.001), and total-body BMD decreased by 1.2 +/- 1.2%; these changes were significantly different from those in the WM group (P < 0.05). Serial measurements showed chronically elevated rates of bone resorption and formation during energy restriction that were greater than in the WM group (P < 0.05). Serum sex hormone binding globulin increased and leptin decreased with weight loss (P < 0.05). Serum PTH tended to increase in the WL group but not in the WM group (P < 0.06). The reduction in fat mass with weight loss was directly associated with a decrease in serum estrone (P < 0.01, R(2) = 0.50). CONCLUSIONS: Moderate energy restriction increases bone turnover in obese postmenopausal women and may be regulated in part by alterations in serum PTH and estrone.

Radioimmunoassay and the hormones of thyroid function.

Radioimmunoassay (RIA) has provided the tools for wide-reaching investigations that have changed and continue to change many important concepts of thyroid physiology and pathosphysiology. The RIA vor human thyrotropin (TSH) was developed in 1965; development of the RIA for triiodothyronine (T3), thyroxine (T4), thyroxine-binding globulin (TBG), and, recently, thyrothropin-releasing hormone (TRH) and thyroglobulin (Tg) followed. The capacity to measure nanogram and picogram concentrations with relative ease and speed has permitted the demonstration of dynamic relationships of the intrathyroidal and circulating thyroid hormones to each other and to the pituitary and hypothalamic regulating hormones. Evidence for the presence of cross-influences between TRH and other hypothalamic regulating hormones on the secretion of pituitary hormones has accumulated. The impact of the new information on clinical practice is now becoming evident. There is new appreciation of the value of assaying serum T3 and TSH concentrations in the clinical management of patients with disturbed function of the thyroid, pituitary, or hypothalamus. The necessary components for RIA performance can be purchansed separately or in kit form from commercial sources. With appropriate quality-control procedures, precise, sensitive, and reliable data can be generated. Awareness of the specific technical problems relating to the RIA of these hormones is absolutely necessary to assure reliable results. The availability of kits or their components permits the performance of these studies in the community hospital and in reliable commercial-service laboratories.

Phylogenetic diversity of the expression of the microtubule-associated protein tau: implications for neurodegenerative disorders.

The microtubule-associated protein tau regulates the dynamic stability of the neuronal cytoskeleton by interacting with microtubules. It is encoded by a single gene, but expressed in a variety of isoforms due to differential RNA splicing. Six isoforms can be found in the human central nervous system. These isoforms differ in their ability to promote the assembly of microtubules as well as in their capacity to stabilize existing microtubule structures. Furthermore, some of the isoforms of tau are specifically involved in the pathogenesis of neurodegenerative disorders. Thus, splicing of tau might critically influence the physiological functions of tau protein as well as the pathogenesis of neurodegenerative diseases with tauopathy. The present study addresses the differential expression of the six isoforms of tau in the central nervous system of 12 mammalian species including Homo sapiens. The occurrence of each of the six tau isoforms was highly variable. However, species that were phylogenetically related expressed a similar pattern of tau isoforms. These results suggest a phylogenetic descent of splicing paradigms, which can be matched with known phylogenetic concepts based on morphological and molecular genetical studies. Especially, the unique expression pattern of tau isoforms in the human central nervous system implicates a possible link to the particular vulnerability of humans to neurodegenerative disorders with tauopathy, namely Alzheimer's disease, frontotemporal dementia and Pick's disease.