Improving live weight gain of crossbred Limousin bulls with cassava peel silage.

There is a growing demand for beef products across developing countries. Formulating rations to include locally available waste products has the potential to increase the live weight gain (LWG) of cattle and improve the livelihoods of smallholder farmers; however, upper limit inclusion levels of cassava peel products require investigation. An experiment evaluated the effect of using cassava peel silage (CPS) at the DM inclusion levels of 30, 40, 50, 60 and 70% (with the remainder protein meals and maize stover in the diet) on the LWG of crossbred Limousin × Ongole bulls (269 ±â€¯48.8 kg). Thirty bulls, approximately two years of age, were allocated in a completely randomised block design with six blocks based on initial live weight (LW) and five treatments based on level of CPS. The combination of CPS (with 2% urea of the CPS) and protein meals significantly affected LWG with the highest values obtained at levels of 30 and 50% inclusion of CPS (1.16-1.35 kg/day) (P < 0.05). Polynomial analysis of LWG data revealed the optimal LWG is theoretically achieved at 37% CPS with a LWG of 1.31 kg/day; however, LWG was similar from 30 to 50% inclusion levels and then declined. There was little significant difference at CPS inclusion levels of 30-60%, for DM intake (DMI) which ranged from 2.3 to 2.6% LW, organic matter (OM) digestibility (77.8-81.6%), feed conversion ratio (FCR) (6.56-7.56 kg DM/kg LWG) and feed cost of gain (Indonesia rupiah (IDR)/kg LW 18 612 - 21 398). At a high (70%) level of CPS inclusion, these values were markedly changed when compared to the 30% inclusion level of CPS. Feed treatments did not affect rumen pH, NH3-N, concentration or molar percentage of volatile fatty acids or protozoal population (P < 0.05). Rumen pH measured three hours after morning feed ranged from 6.7 to 6.8 and NH3-N ranged from 14.1 to 19.3 mg NH3-N/dl. It was concluded that inclusion of CPS up to 60% mixed with protein meals and urea and 20% maize stover maximised LWG and profitability of the production system.

Interrelationship between diseases and calving season and their impact on reproductive parameters and milk production of tropical dairy cows.

The interactions between calving season, the occurrence of retained placenta, intrauterine infections (IUI), and early mastitis, and their effects on the reproductive performance and milk yield of Holstein-Friesian cows in a tropical environment were studied using data from 3320 calvings (1948 cows) from two farms in El Salvador. Based on environmental conditions, season of calving was categorized into: quadrimester 1 (November-February), quadrimester 2 (March-June), and quadrimester 3 (July-October) where quadrimester 2 and 3 had the highest ambient temperature and relative humidity, respectively. Cows were classified into 1, 2, and 3 + parities. The effects of quadrimester and of diseases on days to first service, services per conception, days open, interval between services and 305-day milk yield were studied in separated multivariate regressions. The likelihood of experiencing a disease contingent on the calving season and the likelihood of a cow being culled due to poor fertility associated with experiencing a disease were evaluated using logistic regression. Cows calving in quadrimester 2 and 3 were more likely to suffer from IUI and showed poorer reproduction than cows calving in quadrimester 1. Reproduction was more strongly affected by IUI. Mastitis increased the days to first service, days open, and interval between services. Mastitis and IUI also caused a lower 305-day milk yield. Overall, hotter and more humid conditions lead to higher incidence of disease and poorer reproductive performance. The physiological responses that lead to these phenomena should be further studied to understand the interactions between diseases, environmental conditions and reproduction.

Yield of clinically reportable genetic variants in unselected cerebral palsy by whole genome sequencing.

Cerebral palsy (CP) is the most common cause of childhood physical disability, with incidence between 1/500 and 1/700 births in the developed world. Despite increasing evidence for a major contribution of genetics to CP aetiology, genetic testing is currently not performed systematically. We assessed the diagnostic rate of genome sequencing (GS) in a clinically unselected cohort of 150 singleton CP patients, with CP confirmed at >4 years of age. Clinical grade GS was performed on the proband and variants were filtered, and classified according to American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines. Variants classified as pathogenic or likely pathogenic (P/LP) were further assessed for their contribution to CP. In total, 24.7% of individuals carried a P/LP variant(s) causing or increasing risk of CP, with 4.7% resolved by copy number variant analysis and 20% carrying single nucleotide or indel variants. A further 34.7% carried one or more rare, high impact variants of uncertain significance (VUS) in variation intolerant genes. Variants were identified in a heterogeneous group of genes, including genes associated with hereditary spastic paraplegia, clotting and thrombophilic disorders, small vessel disease, and other neurodevelopmental disorders. Approximately 1/2 of individuals were classified as likely to benefit from changed clinical management as a result of genetic findings. In addition, no significant association between genetic findings and clinical factors was detectable in this cohort, suggesting that systematic sequencing of CP will be required to avoid missed diagnoses.

Formulating rations with cassava meal to promote high live weight gain in crossbred Limousin bulls.

Formulating rations with high energy and protein feeds such as cassava and locally sourced protein meals is an important strategy to increase live weight gain (LWG) of crossbred bulls in Indonesia. Current systems of production for Indonesian smallholders fatten bulls using cut and carry. Formulating a diet for an optimal combination of available feeds will increase production and potential profitability for smallholders. An experiment was conducted to evaluate the effect of using cassava meal in the diet at levels of 70C, 60C, 50C, 40C and 30C% (with most of the remainder being the protein meals) on the LWG of Limousin × Ongole bulls so as to determine the optimum combination of cassava meal and protein meals for LWG. Thirty bulls were allocated in a completely randomized block design with 6 blocks based on initial live weight (LW) and 5 treatments based on level of cassava meal. The combination of cassava meal (with 2% urea) and protein meals significantly affected LWG with the highest (1.35 kg/day) recorded at 40C (40% cassava meal, 40% protein meals and 20% maize stover). The LWG and nutrient intake increased curvilinearly with decreasing cassava meal and increasing protein meals (P < 0.05). Measured cassava meal inclusion in the final ration as a consequence of the changes in intake was 60, 56, 47, 37 and 28% for the designated 70C, 60C, 50C, 40C and 30C treatments, respectively. Dry matter intake reached 96 g/kg0.75 per day or equal to 2.24% LW at this 40% level of inclusion. At the 70C treatment with 60% cassava meal and 9% protein meals, DM digestibility (69.1%) was lowest and that value increased as the proportion of cassava meal decreased and was highest at the 40C treatment (75.8%). Feed treatments significantly affected rumen pH, ammonia N (NH3N) and volatile fatty acid concentrations (P < 0.05). There was no significant effect on protozoal population (P > 0.05). Rumen pH ranged from 6.3 to 6.9. It was concluded that a combination of 40% dried cassava meal and 40% protein meals with roughage (20%) maximized intake and LWG and beyond that level of cassava meal inclusion, LWG and intake decreased markedly.

Targeted resequencing identifies genes with recurrent variation in cerebral palsy.

A growing body of evidence points to a considerable and heterogeneous genetic aetiology of cerebral palsy (CP). To identify recurrently variant CP genes, we designed a custom gene panel of 112 candidate genes. We tested 366 clinically unselected singleton cases with CP, including 271 cases not previously examined using next-generation sequencing technologies. Overall, 5.2% of the naïve cases (14/271) harboured a genetic variant of clinical significance in a known disease gene, with a further 4.8% of individuals (13/271) having a variant in a candidate gene classified as intolerant to variation. In the aggregate cohort of individuals from this study and our previous genomic investigations, six recurrently hit genes contributed at least 4% of disease burden to CP: COL4A1, TUBA1A, AGAP1, L1CAM, MAOB and KIF1A. Significance of Rare VAriants (SORVA) burden analysis identified four genes with a genome-wide significant burden of variants, AGAP1, ERLIN1, ZDHHC9 and PROC, of which we functionally assessed AGAP1 using a zebrafish model. Our investigations reinforce that CP is a heterogeneous neurodevelopmental disorder with known as well as novel genetic determinants.

Contemporary factors influencing genetic diversity in the Alaska humpback whitefish Coregonus clupeaformis complex.

Thirteen microsatellite loci were used to address three hypotheses regarding genetic diversity in the humpback whitefish Coregonus clupeaformis complex in Alaska. The test results provided further insight into the factors influencing C. clupeaformis complex population structure and level of genetic variation. First, the microsatellite data did not provide evidence of two spatially distinct Beringian and Eurasian refugial groups as revealed in previous phylogeographic analyses of mitochondrial DNA variation. Rather, the population structure inferred from the microsatellite variation appears to reveal the influence of factors on a more recent time scale, including gene flow among the refugial groups and isolation of some anadromous and freshwater resident populations. Second, anadromous C. clupeaformis complex collections exhibited higher intra-population genetic diversity than freshwater resident collections. This outcome is consistent with previous meta analyses suggesting that freshwater resident populations probably have smaller historical effective population sizes and less conspecific gene flow because the habitat tends to be smaller and supports fewer and smaller populations. Finally, the analysis of contemporary immigration rates was consistent with, but did not provide statistical support for, the hypothesis that gene flow among anadromous C. clupeaformis complex populations along coastal Alaska is influenced by the Alaska Coastal Current. Further studies are needed to evaluate gene flow among coastal Alaska C. clupeaformis complex populations.

No calcitonin change in a person taking dulaglutide diagnosed with pre-existing medullary thyroid cancer.

BACKGROUND: Glucagon-like peptide-1 receptor agonists, such as dulaglutide, exenatide and liraglutide, are approved to treat Type 2 diabetes mellitus. Although these drugs provide substantial glycaemic control, studies in rodents have prompted concerns about the development of medullary thyroid carcinoma. These data are reflected in the US package insert, with boxed warnings and product labelling noting the occurrence of these tumours after clinically relevant exposures in rodents, and contraindicating glucagon-like peptide-1 receptor agonist use in people with a personal or family history of medullary thyroid carcinoma, or in people with multiple endocrine neoplasia type 2. However, there are substantial differences between rodent and human responses to glucagon-like peptide-1 receptor agonists. This report presents the case of a woman with pre-existing medullary thyroid carcinoma who exhibited no significant changes in serum calcitonin levels despite treatment with dulaglutide 2.0 mg for 6 months in the Assessment of Weekly AdministRation of LY2189265 [dulaglutide] in Diabetes-5 clinical study (NCT00734474). CASE REPORT: Elevated serum calcitonin was noted in a 56-year-old woman with Type 2 diabetes mellitus at the 6-month discontinuation visit in a study of long-term dulaglutide therapy. Retroactive assessment of serum collected before study treatment yielded an elevated calcitonin level. At 3 months post-study, calcitonin level remained elevated; ultrasonography revealed multiple bilateral thyroid nodules. Eventually, medullary thyroid carcinoma was diagnosed; the woman was heterozygous positive for a germline RET proto-oncogene mutation. CONCLUSION: The tumour was not considered stimulated by dulaglutide therapy because calcitonin remained stable throughout.

Aerosol climate change effects on land ecosystem services.

A coupled global aerosol-carbon-climate model is applied to assess the impacts of aerosol physical climate change on the land ecosystem services gross primary productivity (GPP) and net primary productivity (NPP) in the 1996-2005 period. Aerosol impacts are quantified on an annual mean basis relative to the hypothetical aerosol-free world in 1996-2005, the global climate state in the absence of the historical rise in aerosol pollution. We examine the separate and combined roles of fast feedbacks associated with the land and slow feedbacks associated with the ocean. We consider all fossil fuel, biofuel and biomass burning aerosol emission sources as anthropogenic. The effective radiative forcing for aerosol-radiation interactions is -0.44 W m-2 and aerosol-cloud interactions is -1.64 W m-2. Aerosols cool and dry the global climate system by -0.8 °C and -0.08 mm per day relative to the aerosol-free world. Without aerosol pollution, human-induced global warming since the preindustrial would have already exceeded the 1.5 °C aspirational limit set in the Paris Agreement by the 1996-2005 decade. Aerosol climate impacts on the global average land ecosystem services are small due to large opposite sign effects in the tropical and boreal biomes. Aerosol slow feedbacks associated with the ocean strongly dominate impacts in the Amazon and North American Boreal. Aerosol cooling of the Amazon by -1.2 °C drives NPP increases of 8% or +0.76 ± 0.61 PgC per year, a 5-10 times larger impact than estimates of diffuse radiation fertilization by biomass burning aerosol in this region. The North American Boreal suffers GPP and NPP decreases of 35% due to aerosol-induced cooling and drying (-1.6 °C, -0.14 mm per day). Aerosol-land feedbacks play a larger role in the eastern US and Central Africa. Our study identifies an eco-climate teleconnection in the polluted earth system: the rise of the northern hemisphere mid-latitude reflective aerosol pollution layer causes long range cooling that protects Amazon NPP by 8% and suppresses boreal NPP by 35%.

Complementary sex determination, inbreeding depression and inbreeding avoidance in a gregarious sawfly.

Although most Hymenoptera reproduce via arrhenotokous haplodiploidy, the underlying genetic mechanisms vary. Of these, the most widespread mechanism appears to be single-locus complementary sex determination (sl-CSD), in which individuals that are diploid and heterozygous at a sex-determining locus are female, and individuals that are homozygous or hemizygous are male. Because inbreeding increases the probability of producing diploid males, which are often sterile or inviable, sl-CSD can generate substantial inbreeding depression. To counteract this, Hymenoptera with traits that promote inbreeding, such as gregariousness, may evolve one or more of the following: inbreeding avoidance, functional diploid males or alternative sex determination mechanisms. Here, we investigate sex determination, inbreeding depression and inbreeding avoidance in Neodiprion lecontei, a gregarious, pine-feeding sawfly in the family Diprionidae. First, via inbreeding experiments and flow cytometry, we demonstrate that this species has CSD. By modeling expected sex ratios under different conditions, we also show that our data are consistent with sl-CSD. Second, via tracking survival in inbred and outbred families, we demonstrate that inbred families have reduced larval survival and that this mortality is partly attributable to the death of diploid males. Third, using a no-choice mating assay, we demonstrate that females are less willing to mate with siblings than nonsiblings. Together, these results suggest that inbreeding depression stemming from CSD has shaped mating behavior in N. lecontei. These results also set the stage for future comparative work that will investigate the interplay between sex determination, ecology and behavior in additional diprionid species that vary in larval gregariousness.

Low incidence of anti-drug antibodies in patients with type 2 diabetes treated with once-weekly glucagon-like peptide-1 receptor agonist dulaglutide.

Therapeutic administration of peptides may result in anti-drug antibody (ADA) formation, hypersensitivity adverse events (AEs) and reduced efficacy. As a large peptide, the immunogenicity of once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide is of considerable interest. The present study assessed the incidence of treatment-emergent dulaglutide ADAs, hypersensitivity AEs, injection site reactions (ISRs), and glycaemic control in ADA-positive patients in nine phase II and phase III trials (dulaglutide, N = 4006; exenatide, N = 276; non-GLP-1 comparators, N = 1141). Treatment-emergent dulaglutide ADAs were detected using a solid-phase extraction acid dissociation binding assay. Neutralizing ADAs were detected using a cell-based assay derived from human endothelial kidney cells (HEK293). A total of 64 dulaglutide-treated patients (1.6% of the population) tested ADA-positive versus eight (0.7%) from the non-GLP-1 comparator group. Of these 64 patients, 34 (0.9%) had dulaglutide-neutralizing ADAs, 36 (0.9%) had native-sequence GLP-1 (nsGLP-1) cross-reactive ADAs and four (0.1%) had nsGLP-1 neutralization ADAs. The incidence of hypersensitivity AEs and ISRs was similar in the dulaglutide versus placebo groups. No dulaglutide ADA-positive patient reported hypersensitivity AEs. Because of the low incidence of ADAs, it was not possible to establish their effect on glycaemic control.

Treponema infection associated with genital ulceration in wild baboons.

The authors describe genital alterations and detailed histologic findings in baboons naturally infected with Treponema pallidum. The disease causes moderate to severe genital ulcerations in a population of olive baboons (Papio hamadryas anubis) at Lake Manyara National Park in Tanzania. In a field survey in 2007, 63 individuals of all age classes, both sexes, and different grades of infection were chemically immobilized and sampled. Histology and molecular biological tests were used to detect and identify the organism responsible: a strain similar to T pallidum ssp pertenue, the cause of yaws in humans. Although treponemal infections are not a new phenomenon in nonhuman primates, the infection described here appears to be strictly associated with the anogenital region and results in tissue alterations matching those found in human syphilis infections (caused by T pallidum ssp pallidum), despite the causative pathogen's greater genetic similarity to human yaws-causing strains.

Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia.

Cerium oxide nanoparticles (nanoceria) are widely used as catalysts in industrial applications because of their potent free radical-scavenging properties. Given that free radicals play a prominent role in the pathology of many neurological diseases, we explored the use of nanoceria as a potential therapeutic agent for stroke. Using a mouse hippocampal brain slice model of cerebral ischemia, we show here that ceria nanoparticles reduce ischemic cell death by approximately 50%. The neuroprotective effects of nanoceria were due to a modest reduction in reactive oxygen species, in general, and ~15% reductions in the concentrations of superoxide (O(2)(•-)) and nitric oxide, specifically. Moreover, treatment with nanoceria markedly decreased (~70% reduction) the levels of ischemia-induced 3-nitrotyrosine, a modification to tyrosine residues in proteins induced by the peroxynitrite radical. These findings suggest that scavenging of peroxynitrite may be an important mechanism by which cerium oxide nanoparticles mitigate ischemic brain injury. Peroxynitrite plays a pivotal role in the dissemination of oxidative injury in biological tissues. Therefore, nanoceria may be useful as a therapeutic intervention to reduce oxidative and nitrosative damage after a stroke.

Absence of the Birt-Hogg-Dubé gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility.

Under conditions of reduced tissue oxygenation, hypoxia-inducible factor (HIF) controls many processes, including angiogenesis and cellular metabolism, and also influences cell proliferation and survival decisions. HIF is centrally involved in tumour growth in inherited diseases that give rise to renal cell carcinoma (RCC), such as Von Hippel-Lindau syndrome and tuberous sclerosis complex. In this study, we examined whether HIF is involved in tumour formation of RCC in Birt-Hogg-Dubé syndrome. For this, we analysed a Birt-Hogg-Dubé patient-derived renal tumour cell line (UOK257) that is devoid of the Birt-Hogg-Dubé protein (BHD) and observed high levels of HIF activity. Knockdown of BHD expression also caused a threefold activation of HIF, which was not as a consequence of more HIF1α or HIF2α protein. Transcription of HIF target genes VEGF, BNIP3 and CCND1 was also increased. We found nuclear localization of HIF1α and increased expression of VEGF, BNIP3 and GLUT1 in a chromophobe carcinoma from a Birt-Hogg-Dubé patient. Our data also reveal that UOK257 cells have high lactate dehydrogenase, pyruvate kinase and 3-hydroxyacyl-CoA dehydrogenase activity. We observed increased expression of pyruvate dehydrogenase kinase 1 (a HIF gene target), which in turn leads to increased phosphorylation and inhibition of pyruvate dehydrogenase. Together with increased protein levels of GLUT1, our data reveal that UOK257 cells favour glycolytic rather than lipid metabolism (a cancer phenomenon termed the 'Warburg effect'). UOK257 cells also possessed a higher expression level of the L-lactate influx monocarboxylate transporter 1 and consequently utilized L-lactate as a metabolic fuel. As a result of their higher dependency on glycolysis, we were able to selectively inhibit the growth of these UOK257 cells by treatment with 2-deoxyglucose. This work suggests that targeting glycolytic metabolism may be used therapeutically to treat Birt-Hogg-Dubé-associated renal lesions.

Effects of arzoxifene on bone, lipid markers, and safety parameters in postmenopausal women with low bone mass.

UNLABELLED: In this Phase 2 study of postmenopausal women with low bone, arzoxifene (a selective estrogen receptor modulator (SERM)) significantly reduced bone turnover marker levels and increased bone mineral density (BMD) versus placebo. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene, a SERM in current clinical use. Arzoxifene's safety profile appeared similar to raloxifene. INTRODUCTION: This 6-month, Phase 2, double-blind, placebo- and raloxifene-controlled study was designed to assess the effects of arzoxifene on bone turnover and overall safety in postmenopausal women with low bone mass. METHODS: Postmenopausal women (N = 219; mean age, 59 years) with a T-score between -1 and -2.5 were randomly assigned to daily arzoxifene 5, 10, 20, or 40 mg, raloxifene 60 mg, or placebo. All received daily calcium. RESULTS: All arzoxifene doses significantly reduced osteocalcin (primary endpoint), type 1 collagen C-telopeptide, bone specific alkaline phosphatase, and procollagen type I amino-terminal propeptide versus placebo, and increased lumbar spine BMD. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene. Arzoxifene decreased cholesterol, low-density lipoprotein cholesterol, and fibrinogen versus placebo. Endometrial thickness change with arzoxifene was not significantly different from placebo or raloxifene; no cases of endometrial hyperplasia or adenocarcinoma were observed. Adverse event reporting with arzoxifene was similar to that with raloxifene, as were hot flush and night sweat reporting. CONCLUSIONS: Arzoxifene suppressed bone turnover and increased BMD. Within the limitations of this study, the endometrial safety profile of arzoxifene appeared similar to that of raloxifene. While no clear dose effect was evident, arzoxifene 20 and 40 mg/day appeared the optimal doses for reducing bone turnover.

A pain assessment tool for patients with limited communication ability.

This article outlines the development and implementation of a multi-dimensional pain assessment tool for use in acute hospitals. The tool can assist nurses in caring for various patient groups, including patients with limited communication.

Structural effects of raloxifene on the proximal femur: results from the multiple outcomes of raloxifene evaluation trial.

INTRODUCTION: Raloxifene improves spine bone mineral density (BMD), and its ability to reduce vertebral fractures by 40-50% suggests that it increases vertebral strength. Positive effects on hip BMD suggest a similar strengthening of the hip, but dimensional ambiguities in BMD by dual energy x-ray absorptiometry (DXA) make it difficult to infer strength effects directly. Hip fractures may be too infrequent to evaluate in practical clinical trials; even the Multiple Outcomes of Raloxifene Evaluation (MORE) study with 7,705 subjects was insufficiently powered to show a comparable reduction in hip fractures. METHODS: An alternative evaluation of hip DXA data in structural terms should provide more direct evidence of treatment effects on hip strength. Hip scans from a subset of the MORE study, including 4,806 postmenopausal women with osteoporosis randomized to daily oral doses of placebo, 60 mg, or 120 mg of raloxifene were reanalyzed by the hip structure analysis (HSA) method. Scans acquired at baseline, 1, 2, and 3 years were evaluated to extract BMD and cross-sectional geometry across the narrowest point on the neck (NN), the intertrochanteric region (IT), and the proximal shaft 1.5 times the minimum neck width distal to the intersection of the neck and shaft axes. RESULTS: While femur outer diameter expanded during follow-up at all three regions, there were no differences in expansion between groups; treatment influenced mainly the amount and distribution of bone within cross-sections. Effects were similar at the two dose levels at the NN region although the 120 mg dose produced a greater effect on section modulus (SM) at the IT region and on BMD, bone cross-sectional area (CSA), SM, average cortical thickness (CT), and buckling ratio (BR) at the shaft region. Compared with placebo after 3 years, treatment groups showed 0.4-2% higher BMD, CSA, SM, and CT and 1-2% lower BR. The smallest treatment effects were evident at the shaft at 60 mg. CONCLUSIONS: We conclude that raloxifene does not influence periosteal apposition in the proximal femur but it nevertheless produces small but significant improvement in resistance to axial and bending stresses (CSA and SM, respectively) at all analyzed regions. The significant reductions in buckling ratio suggest that additional strength loss due to cortical instability is also ameliorated by treatment.

Rapid screening method for detection of bacteria in platelet concentrates.

Public awareness has long focused on the risks of the transmission of viral agents through blood product transfusion. This risk, however, pales in comparison to the less publicized danger associated with the transfusion of blood products contaminated with bacteria, in particular, platelet concentrates. Up to 1,000 cases of clinical sepsis after the transfusion of platelet concentrates are reported annually in the United States. The condition is characterized by acute reaction symptoms and the rapid onset of septicemia and carries a 20 to 40% mortality rate. The urgent need for a method for the routine screening of platelet concentrates to improve patient safety has long been recognized. We describe the development of a rapid and highly sensitive method for screening for bacteria in platelet concentrates for transfusion. No culture period is required; and the entire procedure, from the time of sampling to the time that the final result is obtained, takes less than 90 min. The method involves three basic stages: the selective removal of platelets by filtration following activation with a monoclonal antibody, DNA-specific fluorescent labeling of bacteria, and concentration of the bacteria on a membrane surface for enumeration by solid-phase cytometry. The method offers a universal means of detection of live, nondividing, or dead gram-negative and gram-positive bacteria in complex cellular blood products. The sensitivity is higher than those of the culture-based methods available at present, with a detection limit of 10 to 10(2) CFU/ml, depending upon the bacterial strain.

Effect of raloxifene on bone mineral density and biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis: results from a randomized placebo-controlled trial.

The safety and efficacy of raloxifene, a selective estrogen receptor modulator (SERM), has been studied extensively in large, global clinical trials. However, the effect of raloxifene on bone mineral density (BMD) and on biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis has not been rigorously evaluated. This study was designed to assess the safety and efficacy of raloxifene in Japanese postmenopausal women with osteoporosis following 1 year of therapy. Participants in this multicenter trial were randomly assigned to receive placebo, raloxifene 60 mg/day (RLX60), or raloxifene 120 mg/day (RLX120). Lumbar spine BMD was measured at baseline, 24, 40, and 52 weeks, and biochemical markers of bone turnover were assessed at baseline, 12, 24, and 52 weeks. Serum lipids were assessed at baseline, 12, 24, 40, and 52 weeks, and breast examinations and transvaginal ultrasound of the endometrium were performed at enrollment and 52 weeks. Compared with baseline, women taking RLX60 had significant increases in lumbar spine (L2-L4) BMD at 24 weeks (+3.3%, p<0.001) through 52 weeks (+3.5%, p<0.001) of therapy, and similar results were observed in the RLX120 group. Markers of bone turnover and total cholesterol and LDL-C were significantly reduced, and no significant treatment-group difference was observed for patients reporting at least one adverse event following randomization. In addition, there were no reported venous thromboembolic events (VTE) in any treatment group. The results of this study demonstrate that raloxifene is associated with early increases in lumbar spine BMD, has favorable effects on biochemical markers of bone turnover and lipid profile, and is well tolerated in postmenopausal Japanese women.

Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women.

Raloxifene has been shown to increase bone mineral density and reduce the risk of vertebral fracture in postmenopausal women with osteoporosis. In this study, we report the results of the first prospective longitudinal study to evaluate the mean degree of mineralization of bone (MDMB) in a group of patients enrolled in the Multiple Outcomes of Raloxifene Evaluation trial. Patients were randomly assigned to one of three treatment groups: placebo (n = 24), raloxifene 60 mg/d (RLX60; n = 22), or raloxifene 120 mg/d (RLX120; n = 18). All patients received daily calcium (500 mg) and vitamin D(3) (400-600 IU) supplementation for the duration of the study. Iliac crest biopsies were taken at baseline and after 2 yr of treatment. Quantitative microradiography was used to analyze the biopsy specimens and revealed a statistically significant (P < 0.05) mean percentage increase in total MDMB of 7.0, 5.3, and 5% for RLX60-, RLX120-, and placebo-treated patients, respectively, compared with baseline. Raloxifene treatment was found to shift the distribution of total bone mineral to higher values of MDMB (RLX60, 29%; RLX120, 8%) with greater heterogeneity, compared with placebo. The profile of MDMB observed in biopsies after treatment with placebo and raloxifene, compared with baseline, closely resembles physiological premenopausal bone.

Growth hormone for in vitro fertilization.

BACKGROUND: In an effort to improve outcomes of in vitro fertilisation (IVF) cycles the use of growth hormone (GH) has been considered. Most studies investigate the role of GH in normally ovulating infertile women but there is also an interest in the effect of GH on women who respond poorly to ovulation induction and IVF. OBJECTIVES: To assess the effectiveness of GH or growth hormone releasing (GRF) adjuvant therapy, primarily in terms of improving livebirth rate, for women undergoing ovulation induction prior to IVF in (a) patients with no previous history of poor response and (b) patients with a history of poor response. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's trials register (24 March 2003), the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2003), MEDLINE (1966 to Feb 2003), EMBASE (1988 to Feb 2003) and Biological Abstracts (1969 to Feb 2003). Reference lists of articles were also searched. SELECTION CRITERIA: All randomised controlled trials were included if they addressed the research question and provided outcome data for intervention and control subjects. DATA COLLECTION AND ANALYSIS: Assessment of trial quality and extraction of relevant data was performed independently by two reviewers. Validity was assessed in terms of method of randomisation, completeness of follow-up and co-intervention. MAIN RESULTS: Nine studies (401 couples) were included. Three trials concerned patients with no history of poor response to IVF (91 women) and six investigated previous poor responders (302 women). There was no evidence that routine use of GH affected the outcome of livebirth (3 RCTs; OR 1.17, 95% CI 0.38 to 3.59). In women who had previously responded poorly to IVF there was no significant differences in livebirth when combining trials of GH and GRF (4 RCTs; OR 2.42, 95% CI 0.94 to 6.23). However when trials using GH were analysed separately there was an increase in livebirths (3 RCTs; OR 4.37, 95% CI 1.06 to 18.01). There was no significant differences in any adverse events, but these were poorly and inconsistently reported. REVIEWER'S CONCLUSIONS: Although the use of GH in previous poor responders has been found to show a significant improvement in livebirth rate, this result was only just significant. Also, this data is from just three small trials. Therefore, before recommending GH in IVF further research is necessary to fully define its role. Meanwhile GH should only be considered in the context of a clinical trial.