Effects of phytase supplementation and increased nutrient density on growth performance, carcass characteristics, and hypothalamic appetitive hormone expression and catecholamine concentrations in broilers from 1 to 43 days of age.

Two experiments were conducted to evaluate extra-phosphoric effects of phytase and nutrient density on growth performance, meat yield, and hypothalamic appetitive hormone expression and catecholamine concentrations of broilers. Experiment 1 determined differences of digestible amino acid concentrations and AMEn using 256 Yield Plus × Ross 708 broilers (32 cages, 8 birds/cage) fed diets without or with 4,500 phytase units (FTU)/kg inclusion (16 reps/treatment). In Experiment 2, 832 Yield Plus × Ross 708 broilers (32 pens; 26 birds/pen) were provided diets in a 2 × 2 factorial arrangement consisting of 2 nutrient contents (without or with increased density) and 2 phytase inclusions (0 or 4,500 FTU/kg). Increased nutrient density was formulated to contain 0.007, 0.015, 0.013, 0.021, 0.024%, and 61 kcal/kg higher digestible SAA, Lys, Thr, Val, Ile, and AMEn (from Experiment 1) respectively, compared with the control diet. Growth performance was determined at 14, 28, and 40 d of age and carcass characteristics at 41 d of age. At 43 d of age, plasma inositol, hypothalamic appetitive hormone expression, and catecholamine concentrations were determined from 4 birds/pen. Additive effects of phytase inclusion and increased nutrient density resulted in the lowest (P < 0.05) feed conversion from 1 to 40 d of age and the heaviest (P < 0.01) breast meat weights among dietary treatments. Phytase addition numerically increased feed intake (P = 0.06) and BW gain (P = 0.051) compared with birds fed diets without phytase from 1 to 40 d of age. Plasma inositol and dopamine concentrations were 2.3- and 1.2-fold higher (P < 0.01), respectively, in broilers fed phytase-added diets than birds fed diets without phytase inclusion. However, mRNA expression of neuropeptide Y, agouti-related peptide, proopiomelanocortin, cholecystokinin A receptor, ghrelin, and serotonin concentration were not different (P > 0.05) among treatments. These data indicated additive effects of phytase supplementation and increased nutrient density on growth performance and meat accretion of broilers. However, the influence of phytase on feed intake warrants future research.

Organ-specific isoform selection of fatty acid-binding proteins in tissue-resident lymphocytes.

Tissue-resident memory T (TRM) cells exist throughout the body, where they are poised to mediate local immune responses. Although studies have defined a common mechanism of residency independent of location, there is likely to be a level of specialization that adapts TRM cells to their given tissue of lodgment. It has been shown that TRM cells in the skin rely on the uptake of exogenous fatty acids for their survival and up-regulate fatty acid-binding protein 4 (FABP4) and FABP5 as part of their transcriptional program. However, FABPs exist as a larger family of isoforms, with different members selected in a tissue-specific fashion that is optimized for local fatty acid availability. Here, we show that although TRM cells in a range of tissue widely express FABPs, they are not restricted to FABP4 and FABP5. Instead, TRM cells show varying patterns of isoform usage that are determined by tissue-derived factors. These patterns are malleable because TRM cells relocated to different organs modify their FABP expression in line with their new location. As a consequence, these results argue for tissue-specific overlays to the TRM cell residency program, including FABP expression that is tailored to the particular tissue of TRM cell lodgment.

Local heroes or villains: tissue-resident memory T cells in human health and disease.

Tissue-resident memory T (TRM) cells are increasingly associated with the outcomes of health and disease. TRM cells can mediate local immune protection against infections and cancer, which has led to interest in TRM cells as targets for vaccination and immunotherapies. However, these cells have also been implicated in mediating detrimental pro-inflammatory responses in autoimmune skin diseases such as psoriasis, alopecia areata, and vitiligo. Here, we summarize the biology of TRM cells established in animal models and in translational human studies. We review the beneficial effects of TRM cells in mediating protective responses against infection and cancer and the adverse role of TRM cells in driving pathology in autoimmunity. A further understanding of the breadth and mechanisms of TRM cell activity is essential for the safe design of strategies that manipulate TRM cells, such that protective responses can be enhanced without unwanted tissue damage, and pathogenic TRM cells can be eliminated without losing local immunity.

A divergent transcriptional landscape underpins the development and functional branching of MAIT cells.

MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These cells develop intrathymically through a three-stage process, but the events that regulate this are largely unknown. Here, using bulk and single-cell RNA sequencing-based transcriptomic analysis in mice and humans, we studied the changing transcriptional landscape that accompanies transition through each stage. Many transcripts were sharply modulated during MAIT cell development, including SLAM (signaling lymphocytic activation molecule) family members, chemokine receptors, and transcription factors. We also demonstrate that stage 3 "mature" MAIT cells comprise distinct subpopulations including newly arrived transitional stage 3 cells, interferon-γ-producing MAIT1 cells and interleukin-17-producing MAIT17 cells. Moreover, the validity and importance of several transcripts detected in this study are directly demonstrated using specific mutant mice. For example, MAIT cell intrathymic maturation was found to be halted in SLAM-associated protein (SAP)-deficient and CXCR6-deficient mouse models, providing clear evidence for their role in modulating MAIT cell development. These data underpin a model that maps the changing transcriptional landscape and identifies key factors that regulate the process of MAIT cell differentiation, with many parallels between mice and humans.

Significant polyp and early colorectal cancer - SPECC: The role of the Colorectal Cancer Clinical Nurse Specialist (CNS): promoting patient-centred care.

AIMS: The colorectal Clinical Nurse Specialist (CNS) makes an important contribution to the care of individuals diagnosed with a significant polyp and early colorectal cancer (SPECC). METHODS: This paper offers an expert opinion on the role of the CNS in SPECC, informed by relevant literature. RESULTS: A CNS can support the patient through the diagnostic and treatment pathway acting as the patient's advocate as a core member of the multidisciplinary team. They will offer support and information to help patients understand their diagnosis, make choices about their available treatment options and help them to feel prepared for any treatment undertaken. CONCLUSION: By providing care that is respectful of, and responsive to, individual patient preferences, needs and values, the CNS can play an important role in promoting patient-centred care.

STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction.

OBJECTIVE: To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction. DESIGN: A randomised placebo-controlled trial. SETTING: Thirteen maternal-fetal medicine units across New Zealand and Australia. POPULATION: Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks. METHODS: Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first). MAIN OUTCOME MEASURES: The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia. RESULTS: Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and new-onset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75). CONCLUSIONS: Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing. TWEETABLE ABSTRACT: Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm.

Barriers to accessing termination of pregnancy in a remote and rural setting: a qualitative study.

OBJECTIVE: To explore the experiences of women from a remote and rural setting who had a termination of pregnancy (TOP), in relation to any barriers they may have experienced trying to access TOP. DESIGN: Qualitative interview study. SETTING: Scottish Highlands and Western Isles. POPULATION: Women who had undergone TOP in the Scottish Highlands National Health Service between October 2014 and May 2015. METHODS: Sixteen semi-structured, audio-recorded telephone interviews were conducted by a researcher with women who had consented to be interviewed at their initial assessment. Six stages of thematic analysis were followed to explore themes in and across participant accounts. MAIN OUTCOME MEASURES: Themes derived from interview transcripts. RESULTS: Four themes emerged relating to barriers to access and experience: (1) the impact of travel for TOP, (2) temporal factors unique to this population and how they affected women, (3) the attitude of health professionals, notably general practitioners, as a result of local culture, and (4) stigma surrounding TOP and the expectation that abortion will be traumatising. CONCLUSION: Women in remote and rural areas experience barriers to accessing TOP. Prompt referrals, more providers of TOP and tackling stigma associated with TOP could make delivery of this service more equitable and improve women's journey through TOP. TWEETABLE ABSTRACT: Women in remote and rural areas of Scotland face multiple barriers to accessing termination of pregnancy.

Prevalence and severity of dental fluorosis in four English cities.

OBJECTIVE: To assess the prevalence and severity of dental fluorosis in four city-based populations using a robust photographic method with TF index reporting; and to record the aesthetic satisfaction scores of children in all four cities. BASIC RESEARCH DESIGN: Cross sectional epidemiological survey (surveillance). PARTICIPANTS: 1,904 children aged 11-14 years, in four English cities. INTERVENTIONS: Two cities were served by community water fluoridation schemes supplying water at 1mg/l F. The other two cities did not have water fluoridation schemes and had low levels of fluoride naturally present. MAIN OUTCOME MEASURES: The prevalence and severity of dental fluorosis. Scoring was undertaken using high quality digital images by a single calibrated examiner. RESULTS: Data suggest that the prevalence of fluorosis at levels greater than TF2 are broadly similar to previous studies (F 10%, NF 2%), with an apparent increase in the total number of TF1 cases across both fluoridated (41%) and non-fluoridated cities (32%) with a commensurate decrease in TF0 (F 39%, NF 63%). Data suggest that the proportion of children expressing dissatisfaction with the appearance of their teeth is the same in fluoridated and non-fluoridated communities although the reasons for this may differ. CONCLUSIONS: The levels of fluorosis that might be considered of aesthetic concern are low and stable while the increase in TF1 may be due to an increase in self- and professionally-applied fluoride products or the increased sensitivity afforded by the digital imaging system. It is not however a public health problem or concern. Further monitoring appears justified.

Measuring physical activity and sedentary behaviors in women with young children: a systematic review.

Current evidence indicates that women with young children are less active than women without children. In this review the authors investigated the methods of measuring physical activity employed in studies of women with young children (aged 1-5 years) and the associated challenges in measurement. Articles from databases (MEDLINE, OVID, CINAHL, Google Scholar) and manual searches were limited to English peer-reviewed journals published from 1990 to 2010. Studies that included measurement of physical activity in samples of women with young children were selected. Measurement properties were extracted, and original reliability and validity articles were reviewed for physical activity measurement tools used by 15 samples. The evidence base was dominated by self-report measurement tools, many of which assessed leisure-time physical activity only. Use of motion sensors to assess physical activity in this population was limited. It is likely that much of the habitual physical activity performed by women with young children has not been captured by self-report measures. Further investigation should be undertaken using tools that capture adequately all health-enhancing physical activity among women with young children.

1,1- and 1,2-isomers of the diborane(4) compound B(2){1,2-(NH)(2)C(6)H(4)}(2) and a TCNQ Co-crystal of the 1,1-isomer.

The synthesis and X-ray crystal structures of the diborane(4) isomers 1,1-B(2){1,2-(NH)(2)C(6)H(4)}(2) and 1,2-B(2){1,2-(NH)(2)C(6)H(4)}(2) are described together with the results of quantum chemical calculations which shed light on their relative stabilities and degree of aromaticity. Spectroscopic data are also provided for both isomers of the 4-methyl aryl derivative. The compound 1,1-B(2){1-O-2-(NH)C(6)H(4)}(2) has also been prepared and structurally characterised but no evidence was obtained for the corresponding 1,2-isomer. The compound 1,1-B(2){1,2-(NH)(2)C(6)H(4)}(2) forms a co-crystal with TCNQ, the structure of which is also reported.

Total selenium and selenomethionine in pharmaceutical yeast tablets: assessment of the state of the art of measurement capabilities through international intercomparison CCQM-P86.

Results of an international intercomparison study (CCQM-P86) to assess the analytical capabilities of national metrology institutes (NMIs) and selected expert laboratories worldwide to accurately quantitate the mass fraction of selenomethionine (SeMet) and total Se in pharmaceutical tablets of selenised-yeast supplements (produced by Pharma Nord, Denmark) are presented. The study, jointly coordinated by LGC Ltd., UK, and the Institute for National Measurement Standards, National Research Council of Canada (NRCC), was conducted under the auspices of the Comité Consultatif pour la Quantité de Matière (CCQM) Inorganic Analysis Working Group and involved 15 laboratories (from 12 countries), of which ten were NMIs. Apart from a protocol for determination of moisture content and the provision of the certified reference material (CRM) SELM-1 to be used as the quality control sample, no sample preparation/extraction method was prescribed. A variety of approaches was thus used, including single-step and multiple-step enzymatic hydrolysis, enzymatic probe sonication and hydrolysis with methanesulfonic acid for SeMet, as well as microwave-assisted acid digestion and enzymatic probe sonication for total Se. For total Se, detection techniques included inductively coupled plasma (ICP) mass spectrometry (MS) with external calibration, standard additions or isotope dilution MS (IDMS), inductively coupled plasma optical emission spectrometry , flame atomic absorption spectrometry and instrumental neutron activation analysis. For determination of SeMet in the tablets, five NMIs and three academic/institute laboratories (of a total of five) relied upon measurements using IDMS. For species-specific IDMS measurements, an isotopically enriched standard of SeMet (76Se-enriched SeMet) was made available. A novel aspect of this study relies on the approach used to distinguish any errors which arise during analysis of a SeMet calibration solution from those which occur during analysis of the matrix. To help those participants undertaking SeMet analysis to do this, a blind sample in the form of a standard solution of natural abundance SeMet in 0.1 M HCl (with an expected value of 956 mg kg(-1) SeMet) was provided. Both high-performance liquid chromatography (HPLC)-ICP-MS or gas chromatography (GC)-ICP-MS and GC-MS techniques were used for quantitation of SeMet. Several advances in analytical methods for determination of SeMet were identified, including the combined use of double IDMS with HPLC-ICP-MS following extraction with methanesulfonic acid and simplified two-step enzymatic hydrolysis with protease/lipase/driselase followed by HPLC-ICP-IDMS, both using a species-specific IDMS approach. Overall, satisfactory agreement amongst participants was achieved; results averaged 337.6 mg kg(-1) (n = 13, with a standard deviation of 9.7 mg kg(-1)) and 561.5 mg kg(-1) (n = 11, with a standard deviation of 44.3 mg kg(-1)) with median values of 337.6 and 575.0 mg kg(-1) for total Se and SeMet, respectively. Recovery of SeMet from SELM-1 averaged 95.0% (n = 9). The ability of NMIs and expert laboratories worldwide to deliver accurate results for total Se and SeMet in such materials (selensied-yeast tablets containing approximately 300 mg kg(-1) Se) with 10% expanded uncertainty was demonstrated. The problems addressed in achieving accurate quantitation of SeMet in this product are representative of those encountered with a wide range of organometallic species in a number of common matrices.

Determination of tributyltin in marine sediment: Comité Consultatif pour la Quantité de Matière (CCQM) pilot study P-18 international intercomparison.

The capabilities of National Metrology Institutes (NMIs-those which are members of the Comité Consultatif pour la Quantité de Matière (CCQM)of the CIPM) and selected outside "expert" laboratories to quantitate (C(4)H(9))(3)Sn(+) (TBT) in a prepared marine sediment were assessed. This exercise was sanctioned by the 7th CCQM meeting, April 4-6, 2001, as an activity of the Inorganic Analysis Working Group and was jointly piloted by the Institute for National Measurement Standards of the National Research Council of Canada (NRC) and the Laboratory of the Government Chemist (LGC), UK. A total of 11 laboratories submitted results (7 NMIs, and 4 external labs). Two external laboratories utilized a standard calibration approach based on a natural abundance TBT standard, whereas all NMIs relied upon isotope dilution mass spectrometry for quantitation. For this purpose, a species specific (117)Sn-enriched TBT standard was supplied by the LGC. No sample preparation methodology was prescribed by the piloting laboratories and, by consequence, a variety of approaches was adopted by the participants, including mechanical shaking, sonication, accelerated solvent extraction, microwave assisted extraction and heating in combination with Grignard derivatization, ethylation and direct sampling. Detection techniques included ICP-MS (with GC and HPLC sample introduction), GC-MS, GC-AED and GC-FPD. Recovery of TBT from a control standard (NRCC CRM PACS-2 marine sediment) averaged 93.5+/-2.4% ( n=14). Results for the pilot material averaged 0.680+/-0.015 micro mol kg(-1) ( n=14; 80.7+/-1.8 micro g kg(-1)) with a median value of 0.676 micro mol kg(-1). Overall, performance was substantially better than state-of-the-art expectations and the satisfactory agreement amongst participants permitted scheduling of a follow-up Key comparison for TBT (K-28), a Pilot intercomparison for DBT (P-43), and certification of the test sediment for TBT content and its release as a new Certified Reference Material (HIPA-1) with a TBT content of 0.679+/-0.089 micro mol kg(-1) (expanded uncertainty, k=2, as Sn) (80.5+/-10.6 micro g kg(-1)).

Inhibition of cervical ripening by local application of cyclooxygenase 2 inhibitor.

OBJECTIVE: Our goal was to test the hypothesis that the previously demonstrated progesterone-independent prolongation of pregnancy in rats treated with cervical application of the cyclooxygenase 2 inhibitor nimesulide is the result of inhibition of cervical ripening. STUDY DESIGN: Timed-pregnant Sprague-Dawley rats were randomly allocated to treatment with 50 mg nimesulide or vehicle, applied daily on the cervix for 5 days (days 14-18). On day 19 the animals were humanely killed and the cervices were removed. In the first series of experiments the cervices of animals treated with nimesulide (n = 10) or vehicle (n = 10) were examined with a cervimeter, which stretches the cervical tissues in incremental steps of 0.2 mm at 1-minute intervals. A steeper slope through the linear portion of the resulting force-versus-displacement curve indicates more resistance to stretch. In the second series of experiments the cervices of animals treated with nimesulide (n = 11) or vehicle (n = 11) were examined with the Collascope optical device. The cervical content of cross-linked collagen was measured with light-induced fluorescence. The fluorescence spectrum at 390 nm (peak wavelength of the collagen spectrum) was determined. For standardization, the ratio of counts of collagen peak over reference counts was used in the final analyses as an indicator of cross-linked collagen content. RESULTS: Animals treated with cervical application of nimesulide had significantly higher resistance to stretch than controls (slope: 0.2564 +/- 0.1213 vs 0.1387 +/- 0.0652; P =.019). The cervical content of cross-linked collagen was not significantly different between nimesulide-treated animals and controls (light-induced fluorescence ratios: 3.2134 +/- 0.7390 vs 2.7892 +/- 0.8518; P =.227). CONCLUSIONS: Treatment with cervical application of the cyclooxygenase 2 inhibitor nimesulide prevents the physiologic process of cervical ripening in late pregnancy. The inhibition is not the result of changes in cross-linked collagen content. Inhibition of cervical ripening with locally administered cyclooxygenase 2 inhibitor may be a potentially valuable treatment for patients at risk for preterm delivery.

High-performance liquid chromatographic determination of bradykinin in saliva: a critical review and a new method.

Because of difficulties or dubious results with previously published methodologies, a new semi-automated HPLC method with UV absorbance detection was developed and applied to the determination of bradykinin (BK) in human saliva. The new method consisted of an uncomplicated sample preparation involving the addition to saliva of an equal volume of 0.1 M orthophosphoric acid to stabilize BK, vortex-mixing, centrifugation, and separation, followed by chromatography of the supernatant phase on a C8, 150x3.9-mm (I.D.) stainless steel column. The mobile phase was composed of 19% acetonitrile/0.1% trifluoroacetic acid at flow-rate of 0.4 ml/min. Using UV detection at 220 nm, the detection limit was 1 ng/ml for the BK standard, and 7 ng/ml for the assay of endogenous salivary BK. The orthophosphoric acid initially added to the saliva allowed BK to be stabilized from enzymic degradation at 20 degrees C for 5 days and at 4 degrees C for 60 days. Assignment made to the peak with the chromatographic properties of salivary BK was confirmed by HPLC-MS with an electrospray interface. This paper presents a new method that is reproducible, reliable and allows kinetic studies of salivary BK to be performed for clinical investigations.

The hydrophobin EAS is largely unstructured in solution and functions by forming amyloid-like structures.

BACKGROUND: Fungal hydrophobin proteins have the remarkable ability to self-assemble into polymeric, amphipathic monolayers on the surface of aerial structures such as spores and fruiting bodies. These monolayers are extremely resistant to degradation and as such offer the possibility of a range of biotechnological applications involving the reversal of surface polarity. The molecular details underlying the formation of these monolayers, however, have been elusive. We have studied EAS, the hydrophobin from the ascomycete Neurospora crassa, in an effort to understand the structural aspects of hydrophobin polymerization. RESULTS: We have purified both wild-type and uniformly 15N-labeled EAS from N. crassa conidia, and used a range of physical methods including multidimensional NMR spectroscopy to provide the first high resolution structural information on a member of the hydrophobin family. We have found that EAS is monomeric but mostly unstructured in solution, except for a small region of antiparallel beta sheet that is probably stabilized by four intramolecular disulfide bonds. Polymerised EAS appears to contain substantially higher amounts of beta sheet structure, and shares many properties with amyloid fibers, including a characteristic gold-green birefringence under polarized light in the presence of the dye Congo Red. CONCLUSIONS: EAS joins an increasing number of proteins that undergo a disorder-->order transition in carrying out their normal function. This report is one of the few examples where an amyloid-like state represents the wild-type functional form. Thus the mechanism of amyloid formation, now thought to be a general property of polypeptide chains, has actually been applied in nature to form these remarkable structures.

Determination of defensin HNP-1, HNP-2, and HNP-3 in human saliva by using LC/MS.

The mass spectral profiling of saliva by liquid chromatography mass spectrometry in relation to particular types of pain is being examined. The aim is to develop a profile that could be useful for the assessment of patients and their treatment programs, as well as identifying unknown compounds observed in saliva. Defensin human neutrophil peptide-1 (HNP-1) and defensin HNP-2 were identified and confirmed, whereas defensin HNP-3 was tentatively identified. Linear calibration range of defensin HNP-1 and HNP-2 was 0.25 to 3 microg/ml with R(2) values of > 0.99 for both. The detection limit for defensin HNP-1 and HNP-2 was estimated at 0.1 microg/ml. The healthy subjects surveyed in this study had readily measurable salivary concentrations of defensin HNP-1 (8.6 +/- SD 8.0 microg/ml) and defensin HNP-2 (5.6 +/- SD 5.2 microg/ml).

Localization of regulatory protein binding sites in the proximal region of human myometrial connexin 43 gene.

Parturition is preceded by a large increase in gap junctions between myometrial smooth muscle cells. Connexin 43 is the major structural protein of myometrial gap junctions. To explore transcriptional regulation of the myometrial Cx43 gene, we used DNase I footprinting, electrophoretic mobility shift and transient transfection assays to examine a 312 bp promoter region (-164 to +148) of the gene, utilizing human myometrial cell cultures and nuclear extracts. The DNase I studies showed four regions of nucleoprotein interactions. Protection of region 1 (-80 to -31) encompassed an Activator Protein 1 (AP1) (-44 to -36) and two Specificity Protein 1 (Sp1) (-77 to -69 and -59 to -48) consensus sequences. Regions 2 to 4 included the transcription initiation site (-10 to +25), an Ets/NF-kB consensus sequence (+47 to +74) and a TA-rich region (+81 to +101) respectively. Gel mobility shift and supershift assays demonstrated c-Jun and Sp1 binding at the AP1 and Sp1 sites respectively. Promoter mutagenesis and transient transfection analyses combined with Sp1 and c-Jun/c-Fos over-expression studies indicate that both Sp1 and c-Jun are required for maximal promoter activity and, therefore, may positively regulate transcription of myometrial Cx43 during the initiation of labour.

Swallowing disorders in severe brain injury: risk factors affecting return to oral intake.

OBJECTIVE: To determine the incidence and type of swallowing disorders that accompany severe brain injury and to identify factors that affect oral intake. DESIGN: Inception cohort study. SETTING: Level I trauma center. PATIENTS: Consecutively admitted patients with severe brain injury who achieved cognitive levels during admission to assess swallowing and who did not sustain injuries preventing swallowing assessment (n = 54). MAIN OUTCOME MEASURES: Type of swallowing abnormalities and presence of aspiration evident on videofluoroscopic swallow studies (VFSS), days to initiation and achievement of oral feeding, ventilation days, presence of a tracheostomy, and cognitive levels at initiation and achievement of oral feeding. RESULTS: Sixty-one percent of subjects exhibited abnormal swallowing. Loss of bolus control and reduced lingual control occurred most commonly. Aspiration rate was 41%. Normal swallowers achieved oral feeding in 19 days versus 57 days for abnormal swallowers. Rancho Los Amigos (RLA) Level IV was needed for initiation of oral feeding; Level VI was needed for total oral feeding. Risk factors for abnormal swallowing included: lower admission Glasgow Coma Scale (GCS) and RLA scores, presence of a tracheostomy, and ventilation time longer than 2 weeks. Risk factors for aspiration were lower admission GCS and RLA scores. CONCLUSIONS: Swallowing disorders and behavioral/cognitive skills are frequently present in patients with severe brain injury and significantly affect oral intake of food. Persons who swallow abnormally take significantly longer to start eating and to achieve total oral feeding, and they require nonoral supplementation three to four times longer than those who swallow normally.