Does breastfeeding method influence infant weight gain?

OBJECTIVE: To compare the effect of traditional and "baby-led" breastfeeding advice on early infant weight gain and exclusive breastfeeding rates. DESIGN: Longitudinal cohort study: part prospective, part retrospective. SETTING: One UK general practice. PARTICIPANTS: 63 exclusively breastfed infants in two cohorts: 32 babies born before and 31 babies born after a change in breastfeeding advice. INTERVENTION: A change from baby-led to traditional breastfeeding advice. MAIN OUTCOME MEASURES: Primary analysis: comparison of the effectiveness of the intervention (ie, weight gain expressed as standard deviation score gain (SDSG) between birth and 6-8 weeks) and exclusive breastfeeding rates between babies whose mothers received traditional advice and those whose mothers received baby-led advice. Secondary analysis: relevance of feed length (ie, weight gain expressed as SDSG between birth and 6-8 weeks in babies feeding for 10 min or less from the first breast and those feeding for longer than 10 min). RESULTS: The two groups were equivalent with respect to birth weight, gestational age, and parity. PRIMARY OUTCOME: babies whose mothers received the traditional advice were more likely to be exclusively breast fed up to 12 weeks (log rank chi2 = 9.68, p = 0.002) and gained more weight up to 6-8 weeks than those given baby-led advice (mean SDSG 0.41 (95% CI 0.13 to 0.69) vs -0.23 (95% CI -0.72 to 0.27)). Secondary outcome: irrespective of feeding advice given, babies feeding for 10 min or less from the first breast gained more weight by 6-8 weeks than babies feeding for longer than 10 min (mean SDSG 0.42 (95% CI 0.11 to 0.73) vs -0.19 (95% CI -0.64 to 0.26)). CONCLUSIONS: In this study, traditional breastfeeding advice resulted in increased weight gain and increased exclusive breastfeeding rates compared with baby-led advice. Exclusively breastfed babies who had shorter feeds (10 min or less from the first breast) gained more weight.

Anaerobic digestion of space mission wastes.

The technical feasibility of applying leachbed high-solids anaerobic digestion for reduction and stabilization of the organic fraction of solid wastes generated during space missions was investigated. This process has the advantages of not requiring oxygen or high temperature and pressure while producing methane, carbon dioxide, nutrients, and compost as valuable products. Anaerobic biochemical methane potential assays run on several waste feedstocks expected during space missions resulted in ultimate methane yields ranging from 0.23 to 0.30 L g-1 VS added. Modifications for operation of a leachbed anaerobic digestion process in space environments were incorporated into a new design, which included; (1) flooded operation to force leachate through densified feedstock beds; and (2) separation of biogas from leachate in a gas collection reservoir. This mode of operation resulted in stable performance with 85% conversion of a typical space solid waste blend, and a methane yield of 0.3 Lg per g VS added after a retention time of 15 days. These results were reproduced in a full-scale prototype system. A detailed analysis of this process was conducted to design the system sized for a space mission with a six-person crew. Anaerobic digestion compared favorably with other technologies for solid waste stabilization.

[Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine]. / Inhibiteurs spécifiques de la recapture de la sérotonine (ISRS) de deuxième génération: profil de liaison du transporteur de l'escitalopram et de la R-fluoxétine chez l'homme.

BACKGROUND: Single isomers of the selective serotonin reuptake inhibitors citalopram (escitalopram, S-citalopram) and fluoxetine (R-fluoxetine) are currently under development for the treatment of depression and other psychiatric disorders. Previous studies conducted in laboratory animals have revealed that the biological effects on serotonin reuptake for citalopram reside in the S enantiomer. In contrast, both enantiomers of fluoxetine contribute to its biological activity. METHODS: In the present study, the potency and selectivity of escitalopram, R-fluoxetine, and all of the other currently available selective serotonine reuptake ihibitors were compared for binding affinity at the human serotonin, norepinephrine, and dopamine transporters and several select neurotransmitter receptors using radioligand binding assays. RESULTS: Both escitalopram and R-fluoxetine were potent inhibitors of the serotonin transporter (Ki=1,1 and 1,4 nmol/L, respectively). escitalopram was the most serotonin transporter-selective compound tested and was approximately 30 fold more potent than R-citalopram. CONCLUSIONS: As noted previously, paroxetine and sertraline possess moderate affinity (<50 nmol/L) for the human norepinephrine transporter and dopamine transporter, respectively. R-fluoxetine, unlike the other selective serotonin reuptake inhibitors, possesses moderate affinity (Ki=64 nmol/L) for the serotonin 2C receptor. Potential clinical correlates of these unique attributes of escitalopram and R-fluoxetine are discussed. (Biol Psychiatry 2001; 50: 345-350 " 2001 Society of Biological Psychiatry).

Mucopolysaccharidosis VII in a cat.

Mucopolysaccharidosis VII was diagnosed in a domestic shorthair cat from California. The cat was small and had multiple abnormalities, including a small body disproportionate to the size of the skull, angular deformities of the ribs, abnormally short forelimbs, luxating patellas, generalized epiphyseal dysplasia involving the vertebrae and long bones, cuboidal vertebrae, pectus excavatum, subluxation of both hips, osteosclerosis of the tentorium cerebelli and left petrous temporal bone, tracheal hypoplasia, and corneal clouding. Beta-glucuronidase activity was markedly decreased in peripheral blood leukocytes. The cat died at 21 months of age, and a complete necropsy was performed. Tissues were examined by light and transmission electron microscopy. Large clear, round vacuoles representing distended lysosomes were present in many epithelial and connective tissue cells, including fibrocytes, chondrocytes, smooth muscle cells, hepatocytes, astrocytes, and macrophages.

Operative results of the inferior capsular shift procedure for multidirectional instability of the shoulder.

BACKGROUND: Neer and Foster previously described the inferior capsular shift procedure for treating multidirectional instability of the shoulder and reported preliminary results that were quite satisfactory. The purpose of our study was to perform a longer-term follow-up evaluation of the efficacy of the inferior capsular shift procedure for treating multidirectional instability of the shoulder. METHODS: An inferior capsular shift procedure was used to treat multidirectional instability of the shoulder in forty-nine patients (fifty-two shoulders). All patients had failed to respond to an exercise program. In this series, the operative approach (anterior or posterior) was based on the major direction of the instability, as determined by the preoperative history and physical examination and as verified by examination with the patient under anesthesia. In all of the patients, the inferior capsular shift was the primary attempt at operative stabilization. The repair consisted of a lateral-side (or humeral-side) shift of the capsule to reduce capsular redundancy and, when necessary, a reattachment of the avulsed labrum to the anteroinferior aspect of the glenoid. RESULTS: A redundant capsular pouch was seen in all of the shoulders in this series. In addition, detachment of the anteroinferior aspect of the labrum was found in ten shoulders and an anterior fracture of the glenoid rim was seen in two shoulders. At an average of sixty-one months (range, twenty-four to 132 months), results were available for forty-nine shoulders (forty-six patients). Thirty shoulders (61 percent) had an excellent overall result, sixteen (33 percent) had a good result, one (2 percent) had a fair result, and two (4 percent) had a poor result. Forty-seven (96 percent) of the forty-nine shoulders remained stable at the time of follow-up. Two of the thirty-four shoulders that had been repaired through an anterior approach began to subluxate anteroinferiorly again. None of the fifteen shoulders that had been repaired through a posterior approach had recurrent instability. Full function, including the ability to perform strenuous manual tasks, was restored to forty-five shoulders (92 percent). A return to sports was possible after thirty-one (86 percent) of the thirty-six procedures done in athletes; however, a return to the premorbid level of participation was possible after only twenty-five (69 percent) of the thirty-six procedures. CONCLUSIONS: The results in this series demonstrate the efficacy and the durability of the results of the inferior capsular shift procedure for the treatment of shoulders with multidirectional instability. The procedure directly addresses the major pathological feature - a redundant joint capsule. Similar results were seen with either an anterior or a posterior approach, and we continue to approach shoulders with multidirectional instability on the side of greatest instability. A postoperative brace was reserved for patients in whom a posterior approach had been used or in whom an anterior approach had involved extensive posterior capsular dissection (ten of the thirty-four shoulders treated with the anterior approach).

Fosl1 is a transcriptional target of c-Fos during osteoclast differentiation.

Osteoclasts are bone-resorbing cells derived from haematopoietic precursors of the monocyte-macrophage lineage. Mice lacking Fos (encoding c-Fos) develop osteopetrosis due to an early differentiation block in the osteoclast lineage. c-Fos is a component of the dimeric transcription factor activator protein-1 (Ap-1), which is composed mainly of Fos (c-Fos, FosB, Fra-1 and Fra-2) and Jun proteins (c-Jun, JunB and JunD). Unlike Fra-1 (encoded by Fosl1), c-Fos contains transactivation domains required for oncogenesis and cellular transformation. The mechanism by which c-Fos exerts its specific function in osteoclast differentiation is not understood. Here we show by retroviral-gene transfer that all four Fos proteins, but not the Jun proteins, rescue the differentiation block in vitro. Structure-function analysis demonstrated that the major carboxy-terminal transactivation domains of c-Fos and FosB are dispensable and that Fra-1 (which lacks transactivation domains) has the highest rescue activity. Moreover, a transgene expressing Fra-1 rescues the osteopetrosis of c-Fos-mutant mice in vivo. The osteoclast differentiation factor Rankl (also known as TRANCE, ODF and OPGL; refs 8-11) induces transcription of Fosl1 in a c-Fos-dependent manner, thereby establishing a link between Rank signalling and the expression of Ap-1 proteins in osteoclast differentiation.

Epidemiology and pathobiology of bipolar disorder, and their exploration within a complete catchment area population.

Epidemiological and pathobiological findings in bipolar disorder [BP] have often been limited by selection bias and lack of epidemiological representativeness. In a rural, circumscribed catchment area, 'all' patients with BP were identified and assessed. On preliminary analysis, morbid risk [MR] for BP over the area as a whole was 5.0 ± 0.6/1000. The distribution of MR for BP over geographical subregions showed no significant deviation from a statistical model for random occurrences in space by place at birth, in contrast to schizophrenia [SZ], and varied only modestly among males by place at onset. These results imply different etiological factors acting in BP in comparison with SZ, particularly with regard to the role of early versus later life events. In preliminary analyses of psychotic and cognitive features, current severity of positive symptoms was predicted in BP only by increasing dominance of the left hand; negative symptoms by duration of illness and current anticholinergic exposure; poorer general and frontal cognitive function by older age at onset of illness, increasing duration of illness, and current anticholinergic exposure. The finding on handedness suggests disturbance of cerebral asymmetry associated with positive symptoms in BP, while both negative symptoms and cognitive impairment may involve progressive processes. Further analysis of this epidemiologically complete population, including systematic comparisons of BP with schizoaffective disorder and SZ, continues.

Indoor household pesticides: hazardous waste concern or not?

Many indoor household pesticides are efficient and useful tools for a variety of functions necessary to maintain clean, sanitary, and pleasant homes and institutional facilities, and to provide significant public health benefits. They do so by incorporating active ingredients and formulation technology that have not been associated with significant environmental impact in use or when disposed in landfills. Chemical and environmental fate properties, toxicological characteristics, and use patterns of indoor household pesticides that distinguish them from other categories of pesticides which have been associated with environmental contamination should be recognized when HHW policy is debated and established by governmental agencies. Most indoor household pesticides as defined here should not be considered hazardous waste or HHW because those relatively few containers, often no longer full, that have been disposed with MSW over the years have not been associated with environmental contamination. The tiny amounts of those product residues that will reach MSW landfills have been shown, in general, not to have chemical or environmental fate characteristics that would make them susceptible to leaching. Those that do have the potential to leach based on these characteristics, in most cases, do not represent a threat to human health based on toxicological considerations. However, compounds such as propoxur, which are very mobile and relatively persistent in soil and in addition have been associated with significant potential health effects, may be targeted by the screening process as described here and could be selected for further investigation as candidates for special waste management status (such as HHW). Our analysis and recommendations have not been extended to the many types of lawn and garden pesticides that are commonly used by homeowners and are frequently brought to HHW programs. However, their potential for groundwater contamination could also be judged using the same technical considerations as applied in this review to indoor household pesticides. In light of the very high costs of diverting wastes from the MSW stream and into HHW programs, it is recommended that, as a matter of public policy, all categories of household waste that might be considered as HHW be carefully and objectively evaluated for their potential to harm public health or the environment after disposal at MSW landfills.

Fra-1 potentiates osteoclastic differentiation in osteoclast-macrophage precursor cell lines.

c-Fos, a component of the dimeric transcription factor AP-1, is necessary for osteoclast formation. To determine whether c-Fos can substitute for any or all of the stimuli needed for osteoclast induction, we infected osteoclast precursors with retroviral vectors expressing c-Fos or the Fos-related protein, Fra-1. The infected cells were incubated with or without osteoclast-inductive stimuli. Osteoclast formation from retroviral-infected precursors remained completely dependent on osteoclast-inductive stromal cells. Unexpectedly, infection of bipotential osteoclast-macrophage precursor cell lines with retroviruses expressing Fra-1 but not c-Fos caused a 10-100-fold increase in the number of precursors that developed calcitonin receptors associated with an increase in bone resorption. These observations suggest that, in the precursor cell lines, Fra-1 is a limiting factor for full responsiveness to the osteoclast-inductive environment. Fra-1 is therefore likely to play a role in osteoclast differentiation which is distinct from that of c-Fos.

Induction of osteoclast formation by parathyroid hormone depends on an action on stromal cells.

It is believed that parathyroid hormone (PTH) increases the resorptive activity of pre-existing osteoclasts through a primary interaction with cells of the osteoblastic lineage. Much less is known, however, of the mechanisms by which PTH induces osteoclast formation. It is known that osteoclast formation occurs through a contact-dependent interaction between stromal cells and haemopoietic precursors, but it is not known whether PTH acts on stromal cells or precursors to induce osteoclast formation. To address this issue, we compared the ability of haemopoietic cultures to generate osteoclasts, identified as calcitonin receptor positive (CTRP) cells, and to resorb bone in response to PTH and 1,25(OH)2 vitamin D3 (1,25(OH)2D3). We found that when murine haemopoietic tissues were incubated at densities sufficiently high to support haemopoiesis, both PTH and 1,25(OH)2D3 induced bone resorption in bone marrow cells, but in cultures of haemopoietic spleen only 1,25(OH)2D3 induced CTRP cells, and neither hormone induced bone resorption. To determine whether these differences were attributable to differences in stromal cells or haemopoietic precursors, lower densities of haemopoietic spleen cells were incubated on osteoblastic (UMR 106), splenic or bone marrow stromal cells. We found that the behaviour of the cocultures reflected the characteristics and origin of the stromal cells. Thus, the ability of both osteoblastic and splenic stromal cells to induce CTRP cells with 1,25(OH)2D3, while only osteoblastic cells induced osteoclasts with PTH, from the same precursors, suggests that the ability of PTH to induce osteoclastic differentiation cannot be attributed to a hormonal action on osteoclast precursors, but depends on a response in stromal cells.

Contributions to maxima in protein kinase C activation.

In many lipid systems, the activity of protein kinase C (PKC) exhibits a peak followed by a decline as the mol % of one component is increased. In these systems, an increase in one lipid component is always at the expense of another or accompanied by a change in total lipid concentration. Here we report that in saturated phosphatidylserine (PS)/phosphatidylcholine (PC)/diacylglycerol (DAG) mixtures, increasing PS or DAG at the expense of PC revealed an optimal mol % PS, dependent on mol % DAG, with higher mol % PS diminishing activity. The decrease at high mol % PS is probably not attributable simply to more gel-phase lipid due to the higher melting temperature of saturated PS versus PC because a similar peak in activity occurred in unsaturated lipid systems. Increasing the total lipid concentration at suboptimal mol % PS provided the same activity as higher mol % PS at lower total lipid concentration. However, at optimal mol % PS, activity increased and then decreased as a function of total lipid concentration. PKC autophosphorylation also exhibited an optimum as a function of mol % PS, and increasing the PKC concentration increased the mol % PS at which activity decreased, both for autophosphorylation and for heterologous phosphorylation. Formation of two-dimensional crystals of PKC on lipid monolayers also exhibited a peak as a function of mol % PS, and the unit cell size of the crystals formed shifts from 50 x 50 A at low mol % PS to 75 x 75 A at higher PS. Collectively, these data suggest the existence of optimal lipid compositions for PKC activation, with increased quantity of these domains serving to dilute out enzyme-substrate aggregates and/or enzyme-enzyme aggregates on the lipid surface.

Task and training requirements analysis methodology (TTRAM): an analytic methodology for identifying potential training uses of simulator networks in teamwork-intensive task environments.

A methodology designed to identify potential application areas for use of networked simulations is presented. The technique, known as task and training requirements analysis methodology (TTRAM), has been independently applied to the analysis of numerous US military aircraft simulator networking requirements, and appears to effectively discriminate tasks that are prone to skill decay, that are critical to mission success, that require high levels of internal and external teamwork, and that require additional training support.

Two-dimensional crystals of protein kinase C.

Three two-dimensional (2D) crystal forms of protein kinase C (PKC) alpha and three of PKC delta have been grown on lipid monolayers composed of dioleoylphosphatidylcholine: dioleoylphosphatidylserine: (45:50:5 molar ratio). In the absence of DO, two additional 2D crystals of PKC delta are seen, suggesting that the presence of diolein (DO) alters the conformation of intact PKC at the lipid surface. Reconstructions of electron micrographs of these eight lattices show good reproducibility and indicate that several are appropriate for three-dimensional reconstruction to 20 A resolution.

Osteoclast activation: potent inhibition by the bisphosphonate alendronate through a nonresorptive mechanism.

Alendronate, an aminobisphosphonate used in the treatment of osteoporosis, is a potent inhibitor of bone resorption. Its mechanism of action is unknown. Because it localizes to bone surfaces, we compared the sensitivity of components of the resorptive process to incubation on alendronate-coated bone surfaces. We found that bone resorption by osteoclasts isolated from neonatal rat bone was unaffected by alendronate (10(-4) M). Osteoclast production in bone marrow cultures, as assessed by the production of calcitonin-receptor positive cells, was observed even at 10(-4) M, but bone resorption in these cultures was almost completely abolished by 10(-5) M alendronate. The greater sensitivity of osteoclast activation to inhibition by alendronate that these results suggest was supported by similar inhibition of osteoblast-mediated activation of osteoclasts from neonatal rat bone. Thus, activation of osteoclasts by osteoblastic/stromal cells is apparently the most sensitive component of the pathway whereby bone resorption is affected. Moreover, the ability of alendronate to suppress osteoclastic activation does not depend on resorption-mediated release of alendronate from bone surfaces. This ability extends the range of cell types and processes that might be affected by alendronate, beyond those in the immediate vicinity of resorbing cells, to include any cell that comes into contact with alendronate-coated bone surfaces.