Molecular basis for odorant receptor tuning: a short C-terminal sequence is necessary and sufficient for selectivity of mosquito Or8.

A birth-and-death evolutionary model for odorant receptor gene repertoires presumes the creation of repertoires with the capacity for high-level diversity and rapid ligand specificity change. This changes the recognised odour space, directly affecting fitness-related behaviours and ultimately affecting adaptation to new environments and resources. The proximate molecular mechanisms underlying the tuning of odorant receptor repertoires, and thus peripheral olfaction, are unclear. In the present study, we report a concrete example of this model of odorant receptor evolution leading to rapid changes in receptor tuning that leave the peripheral neuronal circuitry intact. We identified a conserved odorant receptor gene in mosquitoes, Or8, which in Culex quinquefasciatus underwent a duplication and inversion event. The paralogues differ in only minor structural changes manifesting at the C-terminus. We assessed the specificity of the paralogous odorant receptors and receptor neurones. We found that the functional tuning of the receptor was indeed reflected in minor differences in amino acid structure. Specifically, we found that enantiomeric specificity of these mosquito Or8 paralogues relies on eight C-terminal amino acids encoded in the final exon of the gene; thus, the birth of a paralogous odorant receptor can change the tuning of the peripheral olfactory system.

Effect of recurrent yohimbine on immediate and post-hoc behaviors, stress hormones, and energy homeostatic parameters.

Evidence from experimental models has suggested that acute activation of brain stress and anxiety pathways impacts subsequent behaviors that are mediated or modulated by limbic circuitry. There have been limited investigations of prior or chronic activation of these pathways on subsequent limbic-mediated behaviors. In this study, we tested whether recurrent administration of the anxiogenic compound yohimbine (YOH) could have post-injection effects on brain activation, stress hormones, and performance in sucrose self-administration and startle response paradigms. Rats received six injections across two weeks of either 2mg/kg YOH or saline. Behavioral evaluation confirmed the continued efficacy of the YOH regimen, and increased adrenal corticosterone (CORT) was observed. Several days following YOH or SAL administration, cFos, CORT and adrenocorticotropin hormone (ACTH), and behavioral performance were measured. cFos was elevated post-YOH in the hippocampus; ventral tegmental area/zona inserta; and central and medial nuclei of the amygdala. This activation is consistent with a sustained effect of YOH to activate fear and anxiety circuitries in the CNS. CORT but not ACTH was elevated in the YOH-rats following startle testing. Self-administration and startle tests suggested an increase of non-specific activity in the post-YOH rats; there was no increase in sucrose self-administration or startle response per se. Our findings suggest that recurrent YOH administration may prove a useful and reliable model for simulating recurrent stress/anxiety, and that enhancements to the paradigm such as higher or more frequent dosing of YOH could yield stronger or more extensive behavioral effects.

The impact of strenuous physical activity on the development of pelvic organ prolapse.

Pelvic organ prolapse is a common gynaecological problem and the mechanisms underlying prolapse development are not yet clear but it is thought that increases in abdominal pressure, such as those routinely involved in heavy lifting and long periods of standing, may cause progressive pelvic floor damage over time. The aim of this study was to investigate the effects of strenuous physical activity on the development of prolapse. A narrative literature review was carried out to investigate the effects of occupation and recreational activity on the pathogenesis of pelvic organ prolapse. A marked paucity of literature relevant to the research question makes it difficult to draw firm conclusions. Further research is greatly needed to explore potentially preventable factors in this frequently occurring condition. The review reveals some evidence linking strenuous physical activity with pelvic organ prolapse but this is neither consistent nor adequately powered to reach any firm conclusions.

The effects of the proportions of dietary macronutrients on the digestibility, post-prandial endocrine responses and large intestinal fermentation of carbohydrate in working dogs.

AIM: To compare the effects of feeding diets varying in the proportions of macronutrients on the digestibility, post-prandial endocrine responses and large intestinal fermentation of carbohydrate in working dogs. METHODS: The apparent digestibility of two test diets, one comprising low-carbohydrate, high-protein dry biscuits (Diet 1), and one comprising high-carbohydrate, low-protein dry biscuits (Diet 2), fed to 12 adult Harrier Hounds (n=5 female), was determined using the indigestible-marker and total-collection methods. Serial breath samples were collected from each dog before and after feeding, and analysed for concentrations of hydrogen. Concentrations of glucose and insulin in plasma were established from serial blood samples obtained after feeding. RESULTS: The apparent dry matter, protein, fat and energy digestibility of Diet 1 were higher, but the carbohydrate digestibility was lower (p<0.05), than those of Diet 2. The apparent digestibility values determined using the total-collection method were lower (p<0.05) for carbohydrates, and tended to be lower for dry matter and energy (p<0.10) than those determined using the indigestible-marker method, but the values for protein and fat digestibility were similar using the two methods of determination. The maximum concentration (Cmax) of hydrogen detected in the breath of the dogs occurred earlier for Diet 1 than Diet 2 (p<0.01). However, the Cmax and area under the curve (AUC) for breath hydrogen were higher in the dogs fed Diet 2 than Diet 1 (p<0.01). The Cmax for glucose and insulin in plasma occurred earlier in dogs fed Diet 2 compared with those fed Diet 1 (p<0.05). However, the Cmax for glucose, and AUC for glucose and for insulin were not different between the two diets. The Cmax for insulin was greater for Diet 2 compared with Diet 1 (p<0.05). CONCLUSIONS: The low-carbohydrate, high-protein diet (Diet 1) appeared to offer certain advantages to working dogs, including higher apparent nutrient digestibility, slower release of glucose into the bloodstream, and reduced large intestinal fermentation of carbohydrate. CLINICAL RELEVANCE: A low-carbohydrate, high-protein diet may be beneficial for specific groups of dogs, including working dogs subjected to prolonged bouts of exercise requiring a sustained energy source, or those with diabetes mellitus requiring better glycaemic control.

The addition of cottonseed hulls to the starter and supplementation of live yeast or mannanoligosaccharide in the milk for young calves.

The objectives of this study were to investigate the effects of the addition of cottonseed hulls (CSH) to the starter and the supplementation of live yeast product (YST) or mannanoligosaccharide product (MOS) to milk, on growth, intake, rumen development, and health parameters in young calves. Holstein (n = 116) and Jersey (n = 46) bull (n = 74) and heifer (n = 88) calves were assigned randomly within sex at birth to treatments. All calves were fed 3.8 L of colostrum daily for the first 2 d. Holstein calves were fed 3.8 L of whole milk, and Jersey calves were fed 2.8 L of whole milk through weaning at 42 d. Calves continued on trial through 63 d. Six treatments were arranged as a 2 x 3 factorial. Calves received either a corn-soybean meal-based starter (21% crude protein and 6% acid detergent fiber; -CSH) or a blend of 85% corn-soybean meal-based starter and 15% CSH (18% crude protein and 14% acid detergent fiber; +CSH) ad libitum. In addition, calves received whole milk with either no supplement (NONE) or supplemented with 3 g/d of mannanoligosaccharide product (MOS) or 4 g/d of live yeast product (YST) through weaning at 42 d. Twelve Holstein steers [n = 6 (per starter type); n = 4 (per supplement type)] were euthanized for collection and examination of rumen tissue samples. Dry matter intake (DMI) was greater for Holstein calves fed +CSH (0.90 kg/d) than -CSH (0.76 kg/d). Final body weight at 63 d of Holstein calves fed +CSH (75.8 kg) was greater than that of those fed -CSH (71.0 kg). Average daily gain (ADG) was greater for Holstein calves fed +CSH (0.58 kg/d) than -CSH (0.52 kg/d). However, Holstein calves fed -CSH had a greater feed efficiency (FE; 0.71 kg of ADG/kg of DMI) than those fed +CSH (0.65 kg of ADG/kg of DMI). Also, Holstein calves fed +CSH had narrower rumen papillae (0.32 mm) compared with those fed -CSH (0.41 mm). There were no significant effects of CSH on DMI, ADG, or FE in Jersey calves. There were no significant effects of YST or MOS on DMI, ADG, FE, or rumen papillae measures in Holstein calves. Jersey calves fed YST or MOS had greater final body weight at 63 d (51.2 kg and 51.0 kg, respectively) than calves fed NONE (47.5 kg). However, there were no significant effects of YST or MOS on DMI, ADG, or FE in Jersey calves.

Developmental histology, segmental expression, and nutritional regulation of somatotropic axis genes in small intestine of preweaned dairy heifers.

Components of the somatotropic axis and nutrition regulate intestinal development and maturation of enterocytes. We measured gene expression in the mucosal layer of small intestine of preweaned dairy heifers to test the hypothesis that feeding increased amounts of protein and fat alters expression of somatotropic axis genes. Twenty-four newborn Holstein heifers were randomly assigned to 1 of 4 milk replacer (MR) diets: (1) 20% CP, 20% fat MR (DM basis) fed at 450 g/d (CON); (2) 28% CP, 20% fat MR fed at 970 g/d (HPLF); (3) 28% CP, 28% fat MR fed at 970 g/d (HPHF); and (4) 28% CP, 28% fat MR fed at 1,460 g/d (HPHF+). Dry calf starter (20% CP, 1.43% fat) was offered free choice. At 64 +/- 3 d of age heifers were killed and intestinal tissues were harvested for RNA isolation and histological examination. We measured the mRNA expression of growth hormone receptor (GHR), insulin-like growth factor-I (IGF-I), IGF-I receptor (IGF-IR), and IGF binding proteins (IGFBP)-1 to -6 in duodenum, jejunum, and ileum by quantitative real-time reverse transcription PCR. Expression of IGFBP-3 mRNA was lowest in the duodenum of HPHF+ and greatest in the ileum of the CON group, whereas expression of IGFBP-4 mRNA was greatest in the jejunum of the HPHF+ group. Expression of IGFBP-5 mRNA was greatest in the CON and lowest in the HPHF+. However, overall diet did not affect expression of GHR, IGF-I, IGF-IR, or IGFBP-1, -2, and -6. Expression of somatotropic axis genes differed among small intestinal locations. The GHR, IGF-IR, IGFBP-1, and IGFBP-5 mRNA were greatest in the ileum. Duodenum produced less IGF-IR, IGF-I, and IGFBP-5 mRNA. Villi were shortest in the ileum, but there was no difference in villus height between the duodenum and jejunum. There was no difference in crypt depth or villus circumference between locations. In conclusion, some components of the somatotropic axis in preweaned dairy heifers are differentially expressed in regions of the small intestine, and the gene expression tended to be affected by dietary protein and fat.

Effects of milk replacer composition on growth, body composition, and nutrient excretion in preweaned Holstein heifers.

Twenty-four newborn Holstein heifer calves were fed 1 of 4 milk replacers (MR): control (20% CP, 21% fat; MR fed at 441 g/d); high protein/low fat (HPLF; 28% CP, 20% fat; MR fed at 951 g/d); high protein/high fat (HPHF; 27% CP, 28% fat; MR fed at 951 g/d); and HPHF MR fed at a higher rate (HPHF+; 27% CP, 28% fat; MR fed at 1,431 g/d). Dry calf starter (20% CP, 1.43% fat) composed of ground corn (44.4%), 48% CP soybean meal (44.4%), cottonseed hulls (11.2%), and molasses (1.0%) was offered free choice. Heifers were obtained from a commercial dairy, blocked by groups of 8 in the order acquired, and randomly assigned to treatments within group. Upon arrival at the research farm, heifers were fed the control for 2 feedings. Treatments were imposed when heifers were 4 +/- 1 d of age. Heifers were on study for 61 +/- 1 d. Body weight and body size measures were taken weekly. Four-day total collection of feed refusals, feces, and urine was initiated at 57 +/- 1 d of age. Heifers were slaughtered at the end of the collection period to evaluate body composition. Preplanned contrasts were used to compare control to all, HPLF to HPHF, and HPHF to HPHF+. Heifers fed the control diet consumed more starter than those fed other treatment diets, but their total dry matter intake and apparent dry matter digestibility were lowest. Fecal output was highest in heifers fed the control diet, whereas urine output and urine N excretion were lowest. Nitrogen intake and urine N excretion were greater for heifers fed HPHF+ compared with HPHF but were not affected by MR fat content (HPLF vs. HPHF). Retention (g/d) of N and P was greater in heifers fed all nutrient-dense diets compared with those fed the control diet, but was not improved by increasing fat in the milk replacer (HPLF vs. HPHF) or by increasing the amount fed. Addition of fat to the milk replacer (HPLF vs. HPHF) increased empty body weight fat content without improving average daily gain or frame measures. Increasing the volume fed (HPHF vs. HPHF+) increased growth rate and empty body weight, but HPHF+ heifers were neither taller nor longer and their carcasses contained more fat. Clear improvements in growth and nutrient retention were observed with more nutrient-dense diets, but most of the improvements were seen with the increased protein intake relative to the control MR; adding fat to the high protein MR did not further improve lean tissue gain.

Effects of milk replacer composition on selected blood metabolites and hormones in preweaned Holstein heifers.

We investigated the effects of increasing dietary protein and energy on concentrations of selected blood metabolites and hormones in Holstein heifers. Twenty-four heifers were fed 1 of 4 milk replacer (MR) diets for 9 wk (n = 6/diet): control [20% crude protein (CP), 21% fat MR fed at 441 g of dry matter (DM)/d], HPLF (28% CP, 20% fat MR fed at 951 g of DM/d), HPHF (27% CP, 28% fat MR fed at 951 g of DM/d), and HPHF+ (27% CP, 28% fat MR fed at 1,431 g of DM/d). Heifers were fed twice daily; water and starter (20% CP, 1.43% fat) were offered free choice and starter orts recorded daily. Serum and plasma aliquots from blood samples collected twice weekly after a 12-h fast were analyzed for insulin-like growth factor (IGF)-I, IGF-binding proteins (IGFBP), growth hormone (GH), insulin, glucose, nonesterified fatty acids, triglyceride, and plasma urea nitrogen concentrations. Only plasma glucose, IGFBP-2, and IGFBP-3 were affected by diet. Dietary treatment differences were only noted when the control was compared with the average of the other 3 diets. The addition of fat to the MR (HPLF vs. HPHF) and increased volume of MR (HPHF vs. HPHF+) had no effect on plasma glucose concentration or relative abundance of IGFBP-2 or IGFBP-3. Heifers fed the control diet had less glucose, greater IGFBP-2, and less IGFBP-3 than the average of the other 3 diets. There was a diet by week interaction for IGF-I. Serum IGF-I concentration in control heifers varied in a quadratic manner with a nadir (20 +/- 4 ng/mL) at wk 4, whereas IGF-I increased linearly in heifers on other diets. Both insulin and triglyceride changed over time in a complex pattern (significant linear and quadratic contrast effects). The greatest concentrations were measured at wk 0.5 with nadirs at wk 6 for both insulin and triglyceride. Serum GH concentration decreased in a linear manner from wk 0.5 to wk 9 in all heifers. Relative abundance of IGFBP-2 was quadratic over time with the greatest amount of IGFBP-2 observed at wk 5. With the exception of glucose, IGF-I, IGFBP-2, and IGFBP-3, the blood variables measured were not influenced by treatment. The IGF-I -GH-IGFBP axis requires further study in heifers to deduce effects of nutrition on hypothalamic regulation of metabolism. We expected to see more treatment differences in concentrations of metabolites involved with protein and fat metabolism. It is likely that the diets used in this study were not diverse enough in composition to elicit such changes or that the efficiency of use of absorbed protein and fat was not different in these animals.

A model of phosphorus digestion and metabolism in the lactating dairy cow.

A dynamic, mechanistic, compartmental model of phosphorus (P) digestion and metabolism was constructed in the Advanced Continuous Simulation Language using conservation of mass principles and mass action kinetics. Phosphorus was assumed to exist in 3 forms: inorganic (Pi), phytic acid (Pp), and organic (excluding phytic acid; Po). All 3 forms were assumed to be present in the digestive tract with absorption of Pi into blood. Inputs to the model were total P intake; Pp, Po, and Pi as proportions of total P; milk yield; rate of salivation (fixed at 239 L/d); and rate of liquid passage from the rumen (fixed at 198 L/d). The model was fitted to 2 experiments from the literature. Derived parameters were well defined by the data. With a mean observed P intake of 75 g/d, total tract P digestibility was 38%. Phytic acid P digestibility in the rumen was 74%, with no additional Pp digestion in the lower tract. Inorganic P and Po digestibility in the lower tract were 48 and 89%, respectively. Flows of Po and Pi from the rumen were 2.4 and 3.0 times greater than intake, respectively. The increase in Po was apparently due to microbial growth. The increase in Pi arose primarily from secretion of Pi into the rumen via salivation where 65% of absorbed P was recycled to the rumen. Milk synthesis used 30% of absorbed Pi, and 1% was excreted in urine. This research suggested that the primary regulation points for maintaining blood P were bone deposition and resorption and absorption from the intestine. However, because bone P balance was related to both dietary P intake and ruminal phytase activity, it is critical to achieve a better understanding of phytate digestibility across several feeds if dietary P is to be reduced below current requirements.

Nitrogen and phosphorus retention and excretion in late-gestation dairy heifers.

The objectives of this study were to evaluate the effects of limit feeding diets containing concentrates or by-products in place of forages on manure and nutrient excretion in growing, gravid heifers. Eighteen Holstein heifers confirmed pregnant were grouped by due date and fed 1 of 3 diets (n = 6 per treatment) for the last 14 wk of pregnancy. Diets were high forage, fed ad libitum (HF); by-product based (BP), fed at the same rate as HF-fed heifers; or low forage (LF), fed at 86% of the HF diet. Diets were designed to supply equal quantities of P, N, and metabolizable energy. Total collection of feces and urine was conducted in wk 14, 10, 6, and 2 prepartum. The HF ration was 90.7% forage, 13.7% crude protein (CP), and contained orchardgrass hay, corn silage, corn grain, soybean meal 44%, and a vitamin-mineral premix. The BP diet was 46.2% forage and 14.0% CP, with 70% of the grain mix space replaced with soybean hulls and cottonseed hulls in a 1:1 ratio, with intake limited to 93% of the dry matter intake (DMI) of HF. The LF ration was 45.3% forage and 17.8% CP, with intake limited to 86% of the DMI of HF. The effect of diet was analyzed with repeated measures, using preplanned contrasts to compare HF with BP and LF with HF and BP. As designed, heifers fed HF and BP had greater DMI than the heifers limit-fed LF, and there was no effect of diet on average daily gain or BW. Intake and digestibility of N were lower, and fecal N excretion was higher, in heifers fed HF and BP than heifers fed LF. Mean feces excretion on both a wet and dry basis was greater for HF heifers compared with BP heifers and less for LF heifers than for HF and BP heifers. Despite differences in urinary output, diet had no effect on urea N excretion, but there was a trend for heifers fed HF and BP rations to excrete less urinary N compared with those fed LF. Compared with HF and BP heifers, LF heifers tended to have lower fecal P excretion and had higher urinary P excretion. Measured manure and urine excretion from heifers fed LF was greater than current American Society of Agricultural and Biological Engineers values, whereas heifers fed HF excreted less manure and urine than predicted. Heifers achieving similar rates of gain from diets differing in forage, grain, and by-product content excreted widely varying quantities of manure.

The essential medicines list for a global patient population.

Thirty years after its inception, the role, audience, and contents of the global Essential Medicines List (EML) are reviewed. Challenges for decision makers in applying the principles of medicine selection based on efficacy, safety, burden of disease, and cost effectiveness are discussed and illustrated with recent decisions of the Expert Committee. Areas of controversy for decision makers are highlighted, and the advocacy role of the EML for both drug procurement and development of quality-assured products is described.

Manure nutrient excretion by lactating cows fed exogenous phytase and cellulase.

The effect of an exogenous phytase and cellulase-containing enzyme formulation on nutrient digestibility and excretion was evaluated in 24 Holstein cows. Cows were fed corn silage- and alfalfa silage-based diets with or without a cellulase-phytase blend for 31 d in a continuous random design. Treatment groups were balanced for parity, days in milk, and mature-equivalent projected milk yield. Diets contained 37% forage, 18.3% crude protein, 35.4% neutral detergent fiber, 18% acid detergent fiber, and 0.42% P (no supplemental P). Cows were fed once daily in Calan doors and milked 2 times daily. Body weight and milk yield were recorded at each milking. Milk samples were collected on d 28 to 31 at 8 consecutive milkings. On d 28 to 31, fecal grab samples were collected every 8 h, with sampling times advanced by 2 h each day. Feces samples were pooled by cow. Feed and feces samples were analyzed for acid detergent lignin (used as an internal marker) and for N, P, neutral detergent fiber, and acid detergent fiber. Days in milk were similar between treatments, and body weight and milk yield were unaffected by treatment. Cows fed the enzyme formulation had reduced fecal dry matter, neutral detergent fiber, and acid detergent fiber excretion and reduced fecal excretion of N and P. Apparent digestibility of dry matter, acid detergent fiber, neutral detergent fiber, and N tended to increase with the enzyme formulation. Addition of an exogenous phytase and cellulase enzyme formulation to diets for lactating cows reduced fecal nutrient excretion.

Maternal obesity in pregnancy: Is it time for meaningful research to inform preventive and management strategies?

The growing epidemic of obesity in our society has become a major public health issue, with serious social and psychological consequences in addition to the physical health implications. Obesity has reached epidemic proportions globally with a similar rise in prevalence among women in the reproductive age group. This has critical consequences for fetal and maternal health in the antepartum, intrapartum and postpartum periods. The aims of this study were to summarise the implications of maternal obesity on maternal, fetal and neonatal health and to recommend good practice guidelines on the management of this problem. The authors highlight the need for good quality interventional research on maternal obesity while identifying avenues with potential scope for future research in this context.

Giving and receiving of gifts between pharmaceutical companies and medical specialists in Australia.

BACKGROUND: This study investigated the 'gift-relationship' between pharmaceutical companies and doctors. METHODS: The study was based on a survey questionnaire of 823 medical specialists from across Australia. The aim of this study was to investigate gifts offered to medical specialists in Australia by pharmaceutical companies, financial support actively sought by medical specialists for activities other than research and to consider what is ethically appropriate. RESULTS: A high percentage of specialists received offers of food (96%), items for the office (94%), personal gifts (51%) and journals or textbooks (50%). Most specialists were invited to product launches, symposia or educational events (75-84%) and 52% received offers of travel to conferences. A high proportion of offers were accepted (66-79%) except invitations to product launches (49%), sponsored symposia (53%) and offers of travel that included partners (27%). Fifteen per cent of specialists requested financial support from pharmaceutical companies for activities and items, including conferences, travel, educational activities, salaries and donations to specific funds. The study outlined guidelines on gifts from pharmaceutical companies and differing standards applying to gifts and grants for travel. We found that, although most gifts and requests for support complied with professional and pharmaceutical industry guidelines, some--including personal gifts, tickets to sporting events, entertainment and travel expenses for specialists' partners--did not. CONCLUSION: To ensure that physicians' judgements are free from real or perceived influence from industry and to maintain public trust, we support a shift towards more conservative standards on gifts and support for travel evident in recent guidelines.

Technical note: technique for dissection and analysis of the rumen in young calves.

This paper discusses a technique used to evaluate rumen development in young calves, including removal, dissection, and analysis of tissue. The method allowed for examination of the different sacs of the rumen (dorsal, ventral, cranial, and caudal) using scanning electron microscopy to measure papillae denseness and histology slides to measure papillae length and width. Computer software was used to produce accurate measurements of papillae. The rumens of young calves were dissected, and samples were taken from the cranial, caudal, ventral, and dorsal sections. Calves were part of a nutrition research study, and dietary treatments did have an effect on development measurements such as length, width, and papillae denseness.

Use of pharmacoeconomics in prescribing research. Part 5: modelling--beyond clinical trials.

This paper provides an overview of modelling in the economic evaluation of pharmaceuticals, reflecting the increasing use of models in analyses prepared for reimbursement applications to national and local drug formularies. The paper seeks to demystify the most commonly encountered modelling techniques (extrapolation, decision analysis, Markov modelling and Monte Carlo simulation), and to provide guidance in assessing the quality of submitted or published modelled economic evaluations.

Use of pharmacoeconomics in prescribing research. Part 3: Cost-effectiveness analysis--a technique for decision-making at the margin.

This is the third Research Note addressing pharmacoeconomics in prescribing research, reflecting the increasing use of economic evaluation in drug purchasing decisions in a variety of settings. In this segment we provide an overview of the theoretical basis, practical application and methodological limitations of cost-effectiveness analysis (CEA).

Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.

BACKGROUND: Most clinical practice guidelines recommend restrictive red cell transfusion practices with the goal of minimising exposure to allogeneic blood (from an unrelated donor). The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers). OBJECTIVES: To examine the evidence on the effect of transfusion thresholds, on the use of allogeneic and/or autologous blood, and the evidence for any effect on clinical outcomes. SEARCH STRATEGY: Trials were identified by: computer searches of OVID Medline (1966 to December 2000), Current Contents (1993 to Week 48 2000), and the Cochrane Controlled Trials Register (2000 Issue 4). References in identified trials and review articles were checked and authors contacted to identify any additional studies. SELECTION CRITERIA: Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where the intervention groups were assigned on the basis of a clear transfusion "trigger", described as a haemoglobin (Hb) or haematocrit (Hct) level below which a RBC transfusion was to be administered. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using criteria proposed by Schulz et al. (1995). Relative risks of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials using a random effects model. MAIN RESULTS: Ten trials were identified that reported outcomes for a total of 1780 patients. Restrictive transfusion strategies reduced the risk of receiving a red blood cell (RBC) transfusion by a relative 42% (RR=0.58: 95%CI=0.47,0.71). This equates to an average absolute risk reduction (ARR) of 40% (95%CI=24% to 56%). The volume of RBCs transfused was reduced on average by 0.93 units (95%CI=0.36,1.5 units). However, heterogeneity between these trials was statistically significant (p<0.00001) for these outcomes. Mortality, rates of cardiac events, morbidity, and length of hospital stay were unaffected. Trials were of poor methodological quality. REVIEWER'S CONCLUSIONS: The limited published evidence supports the use of restrictive transfusion triggers in patients who are free of serious cardiac disease. However, most of the data on clinical outcomes were generated by a single trial. The effects of conservative transfusion triggers on functional status, morbidity and mortality, particularly in patients with cardiac disease, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells.

Ikirara insertions reveal five new Anopheles gambiae transposable elements in islands of repetitious sequence.

Characterization of Anopheles gambiae genomic clones containing Ikirara inverted repeats revealed five novel sequences related to known transposable elements (TEs). One TE is related to the mariner/Tc1 superfamily of class II (DNA-to-DNA) transposons, while four are related to class I (RNA-mediated transposition) elements. Crusoe, the class II element; is most similar to the Caenorhabditis elegans transposon Tc1-like TEs. Vash elements, represented twice in our clones, are related to the Q/T1 family of A. gambiae non-LTR retrotransposable elements. Guildenstern is a member of the RT1 and RT2 non-LTR retrotransposon family. Although RT1 and RT2 elements normally have a highly stereotyped insertion preference for sequences within ribosomal genes, Guildenstern is not located in ribosomal sequence. JuanAg is the first anopheline member of the mosquito non-LTR retrotransposon family of Juan elements that previously had included just the culicine elements JuanA and JuanC. Approximately 753 bp is missing from the central portion of the JuanAg reverse transcriptase gene, where an Ikirara inverted repeat is found in its stead. Ozymandias, the only LTR retrotransposon found in the clones, is most similar to the Drosophila melanogaster 412 element. Single Ikirara inverted repeats were also found adjacent to nontransposable element repetitious sequences. Our analysis suggests that the A. gambiae genome organization could best be described as islands of short-period interspersion repetitious DNA in a sea of long-period interspersion, mostly unique sequence DNA.

Drug information for consumers: should it be disease or medication specific? Results of a community survey.

OBJECTIVE: To investigate the information-seeking behaviour of medicine users. METHODS: A telephone survey and follow-up in-depth interviews of a random sample of the adult population in the Hunter Region, NSW, Australia. The survey sought information on medicine use, information seeking, and satisfaction and understanding of the information received. In-depth interviews examined the barriers and facilitators of information seeking. RESULTS: Seven hundred and eighty-six people completed the telephone survey and 58 completed the follow-up interviews. Over half (51%) of the medicine users sought information, primarily to 'manage' their medicines, such as how to use the medicine. Over 30% of the questions asked by users related to 'therapeutic choices', such as how well the medicine worked for a particular condition. Doctors and pharmacists were the most frequent sources of information. A small proportion (10%) reported a potential unmet need for medicines information by indicating they would have liked to ask a question, but did not, or were dissatisfied with the information they received. Barriers to information seeking included perceptions that health care professionals were 'too busy', and that they were unwilling to provide information. CONCLUSIONS: Physicians and pharmacists continue to play an important role in providing consumers with medicines information. Although the reported level of unmet need was low, a significant proportion identified needs relating to information on therapeutic choice, rather than 'classical' drug information. IMPLICATIONS: Medicines-related information for the public should include advice on comparative performance of drugs, and be provided within the wider framework of general health information.