Sleep duration and disorders in pregnancy: implications for glucose metabolism and pregnancy outcomes.

Humans have an innate requirement for sleep that is intrinsically governed by circadian and endocrine systems. More recently, reduced sleep duration has gained significant attention for its possible contribution to metabolic dysfunction. Significant evidence suggests that reduced sleep duration may elevate the risk for impaired glucose functioning, insulin resistance and type 2 diabetes. However, to date, few studies have determined the implications of reduced sleep duration with regard to glucose control during pregnancy. With the high prevalence of overweight and obesity in women of reproductive age, the occurrence of gestational diabetes mellitus (GDM) is increasing. GDM results in elevated risk of maternal and fetal complications, as well as increased risk of type 2 diabetes postpartum. Infants born to women with GDM also carry a life-long risk of obesity and type 2 diabetes. The impact of reduced sleep on glucose management during pregnancy has not yet been fully assessed and a paucity of literature currently exits. Herein, we review the association between reduced sleep and impaired carbohydrate metabolism and propose how reduced sleep during pregnancy may result in further dysfunction of the carbohydrate axis. A particular focus will be given to sleep-disordered breathing, as well as GDM-complicated pregnancies. Putative mechanisms of action by which reduced sleep may adversely affect maternal and infant outcomes are also discussed. Finally, we will outline important research questions that need to be addressed.

Informed consent in refractive eye surgery: learning from patients and the courts.

Refractive eye laser surgery involves ablation of the cornea using excimer laser to correct short or long sightedness and thus negate the need for glasses and/or contact lenses. With the doctrine of informed consent often central to claims of medical negligence in this area, we examine the attitudes, understanding and recall of patients to consent for refractive surgery and outline the relevant law. 102 patients undergoing first time refractive surgery were analysed to examine their understanding and recall of the consenting process. Only 2 patients remembered all 5 risks outlined preoperatively, while 11 remembered no risks at all. 65% of patients consulted the internet to learn more about the operation. Our study demonstrates that patient understanding and recall remains poor. A signed consent form is not, of itself a full defence to allegations of uninformed consent, and the consent process must be comprehensive.

Tag rugby: a safe alternative? A review of hand injuries sustained playing tag rugby (2007 season).

INTRODUCTION: Tag rugby is a non-contact, seven-a-side, team sport in which each player wears specially designed shorts with velcro 'tags' attached to them. While tag rugby is a relatively new sport it has grown rapidly in popularity. As a result of its increasing popularity an increased frequency of attendances at plastic surgery clinics was observed and it was decided a review of all hand injuries associated with this new sport was required. MATERIALS AND METHODS: A retrospective case note review of all hand injuries occurring during the tag rugby season for 2007 (March-August) was conducted, with any tag rugby-related hand injuries being selected for further examination. RESULTS: Tag rugby, while being a non-contact sport, is certainly not without a definite injury risk with 12 patients having single digit injuries, ranging from tendon avulsions to phalangeal fractures. The mean age of the injured patients was 26.8 years. DISCUSSION: All of the hand injuries were sustained while 'tackling' during regular play, the hand injuries sustained were all treated using well-described methods and all the patients are recovering well. While the risk of a severe, life-threatening injury is unlikely while playing tag rugby, there is a real risk of sustaining a potentially debilitating hand injury.

Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells.

Interleukin (IL)-12 may be secreted as a bioactive T helper type 1 (Th1) cell-inducing heterodimer, as a monomer, or as an antagonistic homodimer. We analyzed the IL-12 produced by mouse splenic dendritic cells (DCs), human thymic DCs, and cultured human monocyte-derived DCs. IL-12 production required both a microbial or T cell-derived stimulus and an appropriate cytokine milieu. The different IL-12 forms were differentially regulated by the cytokines present rather than the stimulus used. IL-4 alone or together with granulocyte/macrophage colony-stimulating factor or interferon gamma effectively enhanced the production of the bioactive heterodimer and selectively reduced the antagonistic homodimer of IL-12. Therefore, IL-4, the major Th2-driving cytokine, provides a negative feedback causing DCs to produce the major Th1-inducing cytokine, bioactive IL-12.

c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription.

Interleukin 12 (IL-12) is a 70-kD proinflammatory cytokine produced by antigen presenting cells that is essential for the induction of T helper type 1 development. It comprises 35-kD (p35) and 40-kD (p40) polypeptides encoded by separate genes that are induced by a range of stimuli that include lipopolysaccharide (LPS), DNA, and CD40 ligand. To date, the regulation of IL-12 expression at the transcriptional level has mainly been examined in macrophages and restricted almost exclusively to the p40 gene. Here we show that in CD8(+) dendritic cells, major producers of IL-12 p70, the Rel/nuclear factor (NF)-kappaB signaling pathway is necessary for the induction of IL-12 in response to microbial stimuli. In contrast to macrophages which require c-Rel for p40 transcription, in CD8(+) dendritic cells, the induced expression of p35 rather than p40 by inactivated Staphylococcus aureus, DNA, or LPS is c-Rel dependent and regulated directly by c-Rel complexes binding to the p35 promoter. This data establishes the IL-12 p35 gene as a new target of c-Rel and shows that the regulation of IL-12 p70 expression at the transcriptional level by Rel/NF-kappaB is controlled through both the p35 and p40 genes in a cell type-specific fashion.

Ionic conductivity of yttrium fluoride and lutetium fluoride.

At the transitions from the low-temperature orthorhombic forms of lutetium fluoride and yttrium fluoride to the high-temperature hexagonal forms, there are increases of several orders of magnitude in the ionic conductivities. In the high-temperature phases the conductivities are comparable to those of typical ionic melts. These fluoride compounds are therefore solid electrolytes.

Solid Electrolyte Behavior of NaMgF3: Geophysical Implications.

In the solid state, NaMgF(3) transforms smoothly with temperature into a solid electrolyte phase; the conductivity is 130 siemens per meter just below the melting point. The isostructural compound MgSiO(3) should behave similarly under conditions obtaining in the earth's lower mantle, and so it is expected that the electrical conductivity in that region is ionic rather than electronic.

Interwoven metal-organic framework on a periodic minimal surface with extra-large pores.

Interpenetration (catenation) has long been considered a major impediment in the achievement of stable and porous crystalline structures. A strategy for the design of highly porous and structurally stable networks makes use of metal-organic building blocks that can be assembled on a triply periodic P-minimal geometric surface to produce structures that are interpenetrating-more accurately considered as interwoven. We used 4,4',4"-benzene-1,3,5-triyl-tribenzoic acid (H(3)BTB), copper(II) nitrate, and N,N'-dimethylformamide (DMF) to prepare Cu(3)(BTB)(2)(H(2)O)(3).(DMF)(9)(H(2)O)(2) (MOF-14), whose structure reveals a pair of interwoven metal-organic frameworks that are mutually reinforced. The structure contains remarkably large pores, 16.4 angstroms in diameter, in which voluminous amounts of gases and organic solvents can be reversibly sorbed.

Energetics of large fullerenes: balls, tubes, and capsules.

First-principles calculations were performed to compare the energies of 29 different fullerene structures, with mass number from 60 to 240, and of eight nonhelical graphite tubes of different radii. A quantity called the planarity, which indicates the completeness of the pi-bonding, is the single most important parameter determining the energetics of these structures. Empirical equations were constructed for the energies of nonhelical tubes and for those fullerene structures that may be described as balls or capsules. For a given mass number, bail-shaped fullerenes are energetically favored over capsular (tube-like) fullerenes.

Potentially modifiable determinants of malnutrition in older adults: A systematic review.

BACKGROUND & AIMS: Malnutrition in older adults results in significant personal, social, and economic burden. To combat this complex, multifactorial issue, evidence-based knowledge is needed on the modifiable determinants of malnutrition. Systematic reviews of prospective studies are lacking in this area; therefore, the aim of this systematic review was to investigate the modifiable determinants of malnutrition in older adults. METHODS: A systematic approach was taken to conduct this review. Eight databases were searched. Prospective cohort studies with participants of a mean age of 65 years or over were included. Studies were required to measure at least one determinant at baseline and malnutrition as outcome at follow-up. Study quality was assessed using a modified version of the Quality in Prognosis Studies (QUIPS) tool. Pooling of data in a meta-analysis was not possible therefore the findings of each study were synthesized narratively. A descriptive synthesis of studies was used to present results due the heterogeneity of population source and setting, definitions of determinants and outcomes. Consistency of findings was assessed using the schema: strong evidence, moderate evidence, low evidence, and conflicting evidence. RESULTS: Twenty-three studies were included in the final review. Thirty potentially modifiable determinants across seven domains (oral, psychosocial, medication and care, health, physical function, lifestyle, eating) were included. The majority of studies had a high risk of bias and were of a low quality. There is moderate evidence that hospitalisation, eating dependency, poor self-perceived health, poor physical function and poor appetite are determinants of malnutrition. Moderate evidence suggests that chewing difficulties, mouth pain, gum issues co-morbidity, visual and hearing impairments, smoking status, alcohol consumption and physical activity levels, complaints about taste of food and specific nutrient intake are not determinants of malnutrition. There is low evidence that loss of interest in life, access to meals and wheels, and modified texture diets are determinants of malnutrition. Furthermore, there is low evidence that psychological distress, anxiety, loneliness, access to transport and wellbeing, hunger and thirst are not determinants of malnutrition. There appears to be conflicting evidence that dental status, swallowing, cognitive function, depression, residential status, medication intake and/or polypharmacy, constipation, periodontal disease are determinants of malnutrition. CONCLUSION: There are multiple potentially modifiable determinants of malnutrition however strong robust evidence is lacking for the majority of determinants. Better prospective cohort studies are required. With an increasingly ageing population, targeting modifiable factors will be crucial to the effective treatment and prevention of malnutrition.

The associations between training load and baseline characteristics on musculoskeletal injury and pain in endurance sport populations: A systematic review.

OBJECTIVES: To determine the associations between training load, baseline characteristics (e.g. age or previous injury) and rate of musculoskeletal injury and/or pain specifically within an Endurance Sporting Population (ESP). DESIGN: Prospectively registered systematic review. METHODS: Eight electronic databases were searched by two independent reviewers. Studies were required to prospectively monitor both (i) training loads and (ii) musculoskeletal injury and/or pain for >3 months. Methodological quality and risk of bias were determined utilising the Critical Skills Appraisal Program (CASP). Reported effect sizes were categorised as small, medium or large. RESULTS: Twelve endurance sport studies were eligible (running, triathlon, rowing). Increased injury and/or pain risk was associated with: (i) high total training distances per week/month (medium effect size) (ii) training frequency <2 sessions/week (medium effect size) and (iii) both low weekly (<2hours/week) and high monthly (large effect size) training durations. None of the studies reported internal training load data or acute:chronic workload ratios. Baseline characteristics found to increase the rate of injury and/or pain included: (i) a history of previous injury (medium effect size), (ii) age >45 years (small effect size), (iii) non-musculoskeletal comorbidities (large effect size), (iv) using older running shoes (small effect size) and (v) non-competitive behaviour. CONCLUSIONS: This review identifies a range of external training load factors and baseline characteristics associated with an increased rate of injury and/or pain within ESPs. There is an absence of research relating to internal training loads and acute:chronic workload ratios in relation to rate of injury and/or pain within ESPs.

Long-term impact of the low-FODMAP diet on gastrointestinal symptoms, dietary intake, patient acceptability, and healthcare utilization in irritable bowel syndrome.

BACKGROUND: The low-FODMAP diet is a frequently used treatment for irritable bowel syndrome (IBS). Most research has focused on short-term FODMAP restriction; however, guidelines recommend that high-FODMAP foods are reintroduced to individual tolerance. This study aimed to assess the long-term effectiveness of the low-FODMAP diet following FODMAP reintroduction in IBS patients. METHODS: Patients with IBS were prospectively recruited to a questionnaire study following completion of dietitian-led low-FODMAP education. At baseline and following FODMAP restriction (short term) only, gastrointestinal symptoms were measured as part of routine clinical care. Following FODMAP reintroduction, (long term), symptoms, dietary intake, acceptability, food-related quality of life (QOL), and healthcare utilization were assessed. Data were reported for patients who continued long-term FODMAP restriction (adapted FODMAP) and/or returned to a habitual diet (habitual). KEY RESULTS: Of 103 patients, satisfactory relief of symptoms was reported in 12% at baseline, 61% at short-term follow-up, and 57% at long-term follow-up. At long-term follow-up, 84 (82%) patients continued an 'adapted FODMAP' diet (total FODMAP intake mean 20.6, SD 14.9 g/d) compared with 19 (18%) of patients following a 'habitual' diet (29.4, SD 22.9 g/d, P=.039). Nutritional adequacy was not compromised for either group. The 'adapted FODMAP' group reported the diet cost significantly more than the 'habitual' group (P<.001) and affected social eating (P<.01) but there was no effect on food-related QOL. Healthcare utilization was similar between both groups. CONCLUSION AND INFERENCES: Low-FODMAP education is effective for long-term IBS management, enables a nutritionally adequate diet, and is broadly acceptable to patients.

Cystoid macular oedema in paediatric aphakia and pseudophakia.

AIM: To assess the incidence of cystoid macular oedema (CMO), following lensectomy, anterior vitrectomy (limbal and pars plicata), and primary posterior capsulorhexis following surgery for congenital and developmental cataract. METHODS: A prospective study was carried out involving 30 eyes (20 children) with cataract. Lensectomy, primary posterior capsulorhexis, and anterior vitrectomy were performed on all eyes. Vitrectomy was performed using either a limbal or pars plicata approach. Fluorescein angiography was carried out 4-7 weeks after surgery. Fluorescein was administered intravenously and visualised using the Retcam. RESULTS: Anterior vitrectomy was carried out via the limbal approach in 12 eyes and, of these, six were implanted with an intraocular lens. The pars plicata approach was carried out in 18 eyes and 10 received an implant. CMO was not detected in any eye. CONCLUSION: CMO was not detected in the early postoperative period irrespective of approach to anterior vitrectomy or presence of an intraocular lens. Intravenous fluorescein angiography was performed without complication.

Five year follow up of laser in situ keratomileusis for all levels of myopia.

AIMS: To assess the long term refractive and visual outcome of patients who have laser in situ keratomileusis (LASIK) surgery. METHODS: This was a retrospective study of visual and refractive outcome of patients who had LASIK surgery performed in 1998 and 1999. All levels of myopia were included in the study. 49 patients attended for follow up. The main outcome measures were safety, predictability, efficacy, and stability. Postoperative complications and aberrations were also recorded. The mean preoperative spherical equivalent was -4.85. RESULTS: At 2 months postoperatively 67% of eyes were within plus or minus 0.5D of attempted correction with 81% within plus or minus 1.0D. At 5 years postoperatively 60% of eyes were within plus or minus 0.5D of attempted correction with 83% within plus or minus 1.0D. 88% of eyes had a vision of 6/12 or better at 2 months compared to 89% of eyes at 5 years. Best spectacle corrected visual acuity (BSCVA) was unchanged or improved in 51%. No eye lost more than one line of BSCVA. Overall, there was regression towards myopia with a mean change in refraction of -0.5D over the 5 years. As expected, severely myopic patients regressed more with a mean change of -1.06D. However, there was a high level of patient satisfaction with the surgery. CONCLUSION: LASIK surgery offers predictable results in terms of refractive and visual outcome with mild regression in refraction over time.

Molecular cloning of a C-type lectin superfamily protein differentially expressed by CD8alpha(-) splenic dendritic cells.

Dendritic cells (DC) are potent antigen presenting cells that activate naive T cells. It is becoming increasingly clear that DC are not a homogeneous cell population, but comprise different subpopulations that differ in ontogeny and function. To further the molecular characterisation of DC, we screened for genes that were differentially expressed amongst DC subsets and could therefore give insight into their varying biological functions. Using Representational Difference Analysis (RDA) we identified a gene (CIRE) that is expressed at higher levels in the myeloid-related CD8alpha(-) DC than in the lymphoid-related CD8alpha(+) DC. CIRE is a 238 amino acid type II membrane protein, of approximately 33 kDa in size, whose extracellular region contains a C-type lectin domain. Northern blot analysis revealed that CIRE is almost exclusively expressed in DC and was not detected in organs such as heart, brain, kidney, liver, and thymus. T cells failed to express message for CIRE, whilst B cells expressed very low levels. These data here further substantiated by Northern blot analysis of 18 cell lines of various origins (myeloid, macrophage, B and T cell) where only one cell line, which was of myeloid origin and could give rise to DC, expressed mRNA for CIRE. Semi-quantitative RT-PCR suggested that CIRE is down-regulated upon activation. CIRE shares 57% identity with human DC-SIGN, a molecule that has been shown to be the ligand of ICAM-3 and that is also a receptor that binds HIV and facilitates trans-infection of T cells.

Effect of granulocyte-macrophage colony-stimulating factor on the generation of epidermal Langerhans cells.

The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and Flt3 ligand in the in vivo development of Langerhans cells (LC) was assessed, considering both the steady-state levels of LC in the epidermis and the rate of LC recovery after depletion following lipopolysaccharide (LPS) treatment. The density of LC was determined by counting following IA-specific immunofluorescent staining of epidermal sections from mouse ears. LC levels were compared in beta common chain receptor null (beta c(-/-)) mice that fail to respond to GM-CSF interleukin-5 (IL-5), in GM-CSF transgenic mice with elevated GM-CSF levels, and in mice given daily injections of Flt3 ligand. In the steady state, LC levels were increased in GM-CSF transgenic mice and present at reduced levels in beta c(-/-) mice but unchanged in Flt3 ligand-injected mice. Application of LPS to the ears of control BL/6 mice led to an approximately 70% reduction in LC 4 days later, with recovery beginning by day 8 and a return to normal levels by 2 weeks. This recovery was significantly delayed in beta c(-/-) mice and unchanged in Flt3 ligand-injected mice. These results suggest that GM-CSF (but not Flt3 ligand) enhances recruitment/maturation of LC even though GM-CSF is not essential for their formation.

Methods for generation of monoclonal antibodies to the very small drug hapten, 5-benzimidazolecarboxylic acid.

Drug-specific monoclonal antibodies (MAbs) were produced against the very small drug hapten (162.15 Da), 5-benzimidazolecarboxylic acid, an analogue of 2-(4-Thiazolyl)benzimidazole (TBZ) but lacking the thiol group. TBZ is widely used as a broad-spectrum anthelmintic in various animal species and humans and also as a food preservative and agricultural fungicide. The anti-5-benzimidazolecarboxylic acid antibodies produced have potential use for extraction and/or detection of protein-bound residue forms of TBZ. Three in vivo immunisation regimes (with combinations of two related small drug haptens and two different adjuvants/carrier molecules) and an in vitro immunisation procedure using a combination of three related unconjugated small drug haptens were investigated. Specificity for the hapten immunogen/s was initially determined using two different ELISA procedures. BIACORE analysis, in conjunction with drug binding inhibition studies, was used to confirm the specificity of a small number of selected clones. In vivo immunisation with a drug molecule conjugated to a lipopeptide/T-cell epitope, which acts both as a carrier molecule and an adjuvant was the most useful of the methods tested for the production of specific MAbs to a typically very small hapten with low immunogenic properties.

Preliminary evaluation of a lateral flow immunoassay device for screening urine samples for the presence of sulphamethazine.

A lateral flow immunoassay (LFIA) device was developed and applied to testing urine samples for residues of the antimicrobial sulphamethazine (SMZ). This report describes the preparation of a rat monoclonal antibody to SMZ and its characterisation in an ELISA format. Apart from SMZ, the antibody showed high (> or =50%) cross-reactivity to N4-acetyl-sulphamethazine (55%), sulphamerazine (59%) and sulphisoxazole (50%) and lower cross-reactivity of 18% to sulphachlorpyridazine and sulphadiazine. The LFIA device consisted of a nitrocellulose membrane spotted with SMZ-ovalbumin and goat anti-mouse antibody as capture line and control line, respectively. Mouse anti-rat IgG F(ab')2 fragment specific antibody, adsorbed to colloidal carbon, was used as the detection ligand in the LFIA. The LFIA device had a cut-off value of 6.3 ng/ml in diluted (1/10) urine. Urine samples from SMZ-treated pigs, and bovine and porcine urine samples fortified with SMZ were used for a blind, four-laboratory evaluation of the performance of the LFIA device. Concentrations of SMZ in the test samples (n=29), as determined by LC-MS/MS, ranged from 0 (<3) to 1174 ng/ml. The evaluation of the LFIA device showed an overall sensitivity of 100%, a specificity of 71%, and positive and negative prediction values of 73% and 100%, respectively. The LFIA device has been fabricated as a test kit for determining SMZ residues in animals produced for slaughter.

Effects of mecamylamine on human cigarette smoking and subjective ratings.

Multiple measures of cigarette smoking, subjective effect and physiological effect were collected during 90-min test sessions in normal volunteers. Before sessions subjects received oral doses of mecamylamine (2.5, 5.0, 10, 20 mg) or placebo. Each dose and placebo was given three times in a randomized block sequence. Mecamylamine increased several measures of cigarette smoking, including number of cigarettes, number of puffs per cigarette, and expired air carbon monoxide level. Mecamylamine also produced modest, dose-related decreases in standing blood pressure and increases in standing heart rate. The subjective effects produced by mecamylamine were not characteristic of those of psychoactive drugs. Mecamylamine appears to have increased cigarette smoking by decreasing the effective dose level of nicotine available from cigarette smoking.