Hypertension, snoring, and obstructive sleep apnoea during pregnancy: a cohort study.

OBJECTIVE: To assess the frequency of obstructive sleep apnoea among women with and without hypertensive disorders of pregnancy. DESIGN: Cohort study. SETTING: Obstetric clinics at an academic medical centre. POPULATION: Pregnant women with hypertensive disorders (chronic hypertension, gestational hypertension, or pre-eclampsia) and women who were normotensive. METHODS: Women completed a questionnaire about habitual snoring and underwent overnight ambulatory polysomnography. MAIN OUTCOME MEASURES: The presence and severity of obstructive sleep apnoea. RESULTS: Obstructive sleep apnoea was found among 21 of 51 women with hypertensive disorders (41%), but in only three of 16 women who were normotensive (19%, chi-square test, P=0.005). [Author correction added on 16 June 2014, after first online publication: Results mentioned in the abstract were amended.] Non-snoring women with hypertensive disorders typically had mild obstructive sleep apnoea, but >25% of snoring women with hypertensive disorders had moderate to severe obstructive sleep apnoea. Among women with hypertensive disorders, the mean apnoea/hypopnoea index was substantially higher in snorers than in non-snorers (19.9±34.1 versus 3.4±3.1, P=0.013), and the oxyhaemoglobin saturation nadir was significantly lower (86.4±6.6 versus 90.2±3.5, P=0.021). Among women with hypertensive disorders, after stratification by obesity, the pooled relative risk for obstructive sleep apnoea in snoring women with hypertension compared with non-snoring women with hypertension was 2.0 (95% CI 1.4-2.8). CONCLUSIONS: Pregnant women with hypertension are at high risk for unrecognised obstructive sleep apnoea. Although longitudinal and intervention studies are urgently needed, given the known relationship between obstructive sleep apnoea and hypertension in the general population, it would seem pertinent that hypertensive pregnant women who snore should be tested for obstructive sleep apnoea, a condition believed to cause or promote hypertension.

Multidisciplinary, multicomponent interventions to reduce frailty among older persons in residents of residential care facilities: a scoping review.

BACKGROUND: Frailty reduction and reversal have been addressed successfully among older populations within community settings. However, these findings may not be applicable to residential care settings, largely due to the complex and multidimensional nature of the condition. Relatively, few attempts at frailty prevention exist in residential settings. This review aims to identify and describe best practice models of care for addressing frailty among older populations in residential care settings. This research also sets out to explore the impact of multidisciplinary health service delivery models on health outcomes such as mortality, hospitalisations, quality of life, falls and frailty. METHODS: A scoping review of the literature was conducted to address the project objectives. Reference lists of included studies, bibliographic databases and the grey literature were systematically searched for literature reporting multidisciplinary, multidimensional models of care for frailty. RESULTS: The scoping review found no interventions that met the inclusion criteria. Of the 704 articles screened, 664 were excluded as not relevant. Forty articles were fully assessed, and while no eligible studies were found, relevant data were extracted from 10 near-eligible studies that reported single disciplines or single dimensions rather than a model of care. The physical, nutritional, medicinal, social and cognitive aspects of the near eligible studies have been discussed as playing a key role in frailty reduction or prevention care models. CONCLUSION: This review has identified a paucity of interventions for addressing and reducing frailty in residential care settings. High-quality studies investigating novel models of care for addressing frailty in residential care facilities are required to address this knowledge gap. Similarly, there is a need to develop and validate appropriate screening and assessment tools for frailty in residential care populations. Health service providers and policy-makers should also increase their awareness of frailty as a dynamic and reversible condition. While age is a non-modifiable predictor of frailty, addressing modifiable factors through comprehensive care models may help manage and prevent the physical, social and financial impacts of frailty in the ageing population.

Association between habitual snoring, middle ear disease, and speech problems in young children with non-syndromic cleft palate anomalies.

The purpose of this study was to investigate the association between habitual snoring (HS), middle ear disease (MED), and speech problems in children with cleft palate. This cross-sectional study included children aged 2.0-7.9 years with non-syndromic cleft palate anomalies. Parents completed the Pediatric Sleep Questionnaire and a questionnaire about MED. Audiograms and speech assessment were also conducted. Ninety-five children were enrolled; 15.2% of families reported HS, 97.6% MED, and 17.1% speech problems. HS (37.5% vs 10.3%, P = 0.007) and early episodes of MED (92.3% vs 58.2%, P = 0.021) were more likely to be reported for children with isolated cleft palate when compared to those with cleft lip and palate. Children with cleft lip and palate had a higher frequency of MED with effusion compared to those with Robin sequence (86.4% vs 57.1%, P = 0.049). The odds ratio for HS in children with ≥1 episode of MED in the last year was 7.37 (95% confidence interval 1.55-35.15, P = 0.012). There was a trend for children with speech problems reported by parents to have HS (30.8% vs 11.5%, P= 0.076). Anatomical factors play a role in the frequency of upper airway symptoms in children with cleft palate. A recent history of at least one episode of MED was associated with an increased frequency of HS.

Eosinophil-nerve interactions and neuronal plasticity in rat gut associated lymphoid tissue (GALT) in response to enteric parasitism.

Intestinal lymphoid tissues and Peyer's patches (PP) are innervated sites of immune surveillance in the gastrointestinal tract. Following infection with F. hepatica, neuronal hyperplasia and significantly increased eosinophil and mast cell trafficking to colonic PP sites were evident in rat tissues. Nerve-eosinophil associations were significantly elevated in infected colon and colonic PP, as were colonic tissue levels of the circulatory recruitment factors IL-5 and eotaxin. Increased immunoreactivity for neuronal plasticity markers GAP-43 and neural cell adhesion molecule (NCAM) was also found in infected tissues. Such neuronal alterations in the PP during enteric parasitism may have functional consequences on particular or pathogen uptake.

Diagnostic potential of the peptide-mediated magnetic separation (PMS)-phage assay and PMS-culture to detect Mycobacterium avium subsp. paratuberculosis in bovine milk samples.

Controlling the spread of Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), in domestic livestock is challenging. Current diagnostic methods lack sufficient sensitivity to detect subclinically infected animals, and thus, better diagnostic methods are needed. This study was carried out to investigate the diagnostic potential of two novel peptide-mediated magnetic separation (PMS)-based tests-a PMS-phage assay and PMS-culture-both of which have been developed and optimized to detect viable MAP cells in bovine milk. Individual milk samples (50 ml) were obtained from 105 "non-infected" and 40 "MAP-infected" animals (classified as such on the basis of prior faecal culture and serum-ELISA results) in three dairy herds and tested in parallel by the PMS-phage assay and PMS-culture. Diagnostic sensitivity (DSe) and specificity (DSp) of the PMS-phage and PMS-culture methods were determined relative to the MAP infection status of the animal contributing the milk sample. The PMS-based tests applied individually showed moderate DSe (PMS-culture 0.250 and PMS-phage assay 0.325) and high DSp (0.962 and 1.000, respectively). When results of the two PMS-based tests were combined, DSe increased substantially to 0.525, and the DSp was calculated to be 0.962. It was concluded that combined application of the PMS-phage assay and PMS-culture provided the most complete picture regarding the presence of viable MAP in bovine milk samples. A comprehensive validation of the PMS-based assays relative to currently used diagnostic methods (faecal culture and serum-ELISA) would be the next step in assessment of the diagnostic potential of these novel PMS-based methods.

Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis.

We report a whole-brain MRI morphometric survey of asymmetry in children with high-functioning autism and with developmental language disorder (DLD). Subjects included 46 boys of normal intelligence aged 5.7-11.3 years (16 autistic, 15 DLD, 15 controls). Imaging analysis included grey-white segmentation and cortical parcellation. Asymmetry was assessed at a series of nested levels. We found that asymmetries were masked with larger units of analysis but progressively more apparent with smaller units, and that within the cerebral cortex the differences were greatest in higher-order association cortex. The larger units of analysis, including the cerebral hemispheres, the major grey and white matter structures and the cortical lobes, showed no asymmetries in autism or DLD and few asymmetries in controls. However, at the level of cortical parcellation units, autism and DLD showed more asymmetry than controls. They had a greater aggregate volume of significantly asymmetrical cortical parcellation units (leftward plus rightward), as well as a substantially larger aggregate volume of right-asymmetrical cortex in DLD and autism than in controls; this rightward bias was more pronounced in autism than in DLD. DLD, but not autism, showed a small but significant loss of leftward asymmetry compared with controls. Right : left ratios were reversed, autism and DLD having twice as much right- as left-asymmetrical cortex, while the reverse was found in the control sample. Asymmetry differences between groups were most significant in the higher-order association areas. Autism and DLD were much more similar to each other in patterns of asymmetry throughout the cerebral cortex than either was to controls; this similarity suggests systematic and related alterations rather than random neural systems alterations. We review these findings in relation to previously reported volumetric features in these two samples of brains, including increased total brain and white matter volumes and lack of increase in the size of the corpus callosum. Larger brain volume has previously been associated with increased lateralization. The sizeable right-asymmetry increase reported here may be a consequence of early abnormal brain growth trajectories in these disorders, while higher-order association areas may be most vulnerable to connectivity abnormalities associated with white matter increases.

Synthesis and biological evaluation of substituted flavones as gastroprotective agents.

Flavone (1) was found to protect against ethanol-induced gastric damage in rats; however, it is known that certain compounds in the flavone class, including flavone itself, are inducers of hepatic drug metabolizing enzymes. With the hope of identifying gastroprotective flavones that have minimal effects on drug metabolizing enzymes, we have synthesized and evaluated selected flavone analogs. Gastroprotective potency in the ethanol model was retained by methoxy substitution in the 5-position (4) and by methoxy (12) or methyl (14) substitution in the 7-position. A number of substituted analogs of the potent molecule 5-methoxyflavone (4) were also synthesized, and in many cases, these substitutions provided gastroprotective molecules. In order to assess liver enzyme induction potential, two of the gastroprotective flavones, 7-methoxyflavone (12) and 5-methoxy-4'-fluoroflavone (26), were examined for their effect on liver microsomal cytochrome P450 and 7-ethoxyresorufin O-dealkylase (CYP1A) activity. These two compounds caused minimal changes in the cytochrome P450 concentration and were considerably less potent than beta-naphthoflavone as inducers of CYP1A enzyme activity. Furthermore, following oral administration to rats, 5-methoxy-4'-fluoroflavone (26) was found to protect against indomethacin-induced gastric damage. These results indicate that, through appropriate substitution, flavones can be obtained that are gastroprotective but have minimal effects on drug-metabolizing enzymes.

Response of Mycobacterium smegmatis to acid stress.

Evidence was sought for the existence of an inducible acid tolerance response in Mycobacterium smegmatis. Exposure of M. smegmatis to a sub-lethal, adaptive acidic pH was found to confer a significant level of protection against subsequent exposure to a lethal pH, compared to unadapted cells. Adaptation was dependent on de novo protein synthesis.

Oxygen saturation during the first 24 hours of life.

AIM: To determine normative data for arterial oxygen saturation, measured by pulse oximetry (SpO2), in healthy full term infants throughout their first 24 hours of life. METHODS: Long term recordings of SpO2, pulse waveform, and breathing movements were made on 90 infants. Recordings were analysed for baseline SpO(2), episodes of desaturation (SpO2 /= four seconds, and periodic apnoea (>/= three apnoeic pauses, each separated by /= 20 seconds) were identified in six recordings. Four desaturations fell to

Preparation of 99Tcm-MAG3: no confirmation that sodium chloride injections from plastic containers affect radiochemical purity.

Reports have suggested that when sodium chloride injections from a plastic ampoule are used during the preparation of 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3), the radiochemical purity of the final product might be reduced. A study was therefore undertaken to examine the effect of sodium chloride injections from five manufacturers on the radiochemical purity and stability of 99Tcm-MAG3. One sodium chloride injection was supplied in a glass vial, three in plastic ampoules and one in a plastic infusion bag. Three batches of sodium chloride injections from each manufacturer were tested. The radiopharmaceutical was prepared at a radioactive concentration of 1.1 GBq in 10 ml according to the instructions of the manufacturer of TechneScan MAG3. Analysis of radiochemical purity was performed by high-performance liquid chromatography immediately after preparation and 6 h later. Using 95% as the minimum acceptable radiochemical purity, all the products were satisfactory over the 6 h test period. No manufacturer's sodium chloride injection was found to have a statistically significant effect on the radiochemical purity. Based on the 15 batches of sodium chloride injection tested, this study cannot confirm that sodium chloride injections from a plastic container affect the radiochemical purity of 99Tcm-MAG3. However, in view of the known sensitivity of some 99Tcm radiopharmaceuticals to external influences, it is probably good practice to test radiochemical purity when new batches of ancillary materials, such as sodium chloride injections, are introduced.

Effect of exposure to 15% oxygen on breathing patterns and oxygen saturation in infants: interventional study.

OBJECTIVE: To assess the response of healthy infants to airway hypoxia (15% oxygen in nitrogen). DESIGN: Interventional study. SETTINGS: Infants' homes and paediatric ward. SUBJECTS: 34 healthy infants (20 boys) born at term; mean age at study 3.1 months. 13 of the infants had siblings whose deaths had been ascribed to the sudden infant death syndrome. INTERVENTION: Respiratory variables were measured in room air (pre-challenge), while infants were exposed to 15% oxygen (challenge), and after infants were returned to room air (post-challenge). MAIN OUTCOME MEASURES: Baseline oxygen saturation as measured by pulse oximetry, frequency of isolated and periodic apnoea, and frequency of desaturation (oxygen saturation < or = 80% for > or = 4 s). Exposure to 15% oxygen was terminated if oxygen saturation fell to < or = 80% for > or = 1 min. RESULTS: Mean duration of exposure to 15% oxygen was 6.3 (SD 2.9) hours. Baseline oxygen saturation fell from a median of 97.6% (range 94.0% to 100%) in room air to 92.8% (84.7% to 100%) in 15% oxygen. There was no correlation between baseline oxygen saturation in room air and the extent of the fall in baseline oxygen saturation on exposure to 15% oxygen. During exposure to 15% oxygen there was a reduction in the proportion of time spent in regular breathing pattern and a 3.5-fold increase in the proportion of time spent in periodic apnoea (P < 0.001). There was an increase in the frequency of desaturation from 0 episodes per hour (range 0 to 0.2) to 0.4 episodes per hour (0 to 35) (P < 0.001). In 4 infants exposure to hypoxic conditions was ended early because of prolonged and severe falls in oxygen saturation. CONCLUSIONS: A proportion of infants had episodes of prolonged (< or = 80% for > or = 1 min) or recurrent shorter (< or = 80% for > or = 4 s) desaturation, or both, when exposed to airway hypoxia. The quality and quantity of this response was unpredictable. These findings may explain why some infants with airway hypoxia caused by respiratory infection develop more severe hypoxaemia than others. Exposure to airway hypoxia similar to that experienced during air travel or on holiday at high altitude may be harmful to some infants.

Sodium butyrate improves locomotor impairment and early mortality in a rotenone-induced Drosophila model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder primarily affecting the dopaminergic neurons in the nigrastriatal pathway resulting in debilitating motor impairment in both familial and sporadic cases. Histone deacetylase (HDAC) inhibitors have been recently implicated as a therapeutic candidate because of their ability to correct the disrupted HDAC activity in PD and other neurodegenerative diseases. Sodium butyrate (SB), an HDAC inhibitor, reduces degeneration of dopaminergic neurons in a mutant alpha-synuclein Drosophila transgenic model of familial PD. Chronic exposure to the pesticide rotenone also causes selective degeneration of dopaminergic neurons and causes locomotor impairment and early mortality in a Drosophila model of chemically induced PD. This study investigated the effects of sodium butyrate on locomotor impairment and early mortality in a rotenone-induced PD model. We show that treatment with 10mM SB-supplemented food rescued the rotenone-induced locomotor impairment and early mortality in flies. Additionally, flies with the genetic knockdown of HDAC activity through Sin3A loss-of-function mutation (Sin3A(lof)) were resistant to rotenone-induced locomotor impairment and early mortality. Furthermore, SB-supplemented Sin3A(lof) flies had a modest additive effect for improving locomotor impairment. We also show SB-mediated improvement of rotenone-induced locomotor impairment was associated with elevated dopamine levels in the brain. However, the possibility of SB-mediated protective role through mechanisms independent from dopamine system is also discussed. These findings demonstrate that HDAC inhibitors like SB can ameliorate locomotor impairment in a rotenone-induced PD model.

The impact of local surface changes in Borneo on atmospheric composition at wider spatial scales: coastal processes, land-use change and air quality.

We present results from the OP3 campaign in Sabah during 2008 that allow us to study the impact of local emission changes over Borneo on atmospheric composition at the regional and wider scale. OP3 constituent data provide an important constraint on model performance. Treatment of boundary layer processes is highlighted as an important area of model uncertainty. Model studies of land-use change confirm earlier work, indicating that further changes to intensive oil palm agriculture in South East Asia, and the tropics in general, could have important impacts on air quality, with the biggest factor being the concomitant changes in NO(x) emissions. With the model scenarios used here, local increases in ozone of around 50 per cent could occur. We also report measurements of short-lived brominated compounds around Sabah suggesting that oceanic (and, especially, coastal) emission sources dominate locally. The concentration of bromine in short-lived halocarbons measured at the surface during OP3 amounted to about 7 ppt, setting an upper limit on the amount of these species that can reach the lower stratosphere.

A carpet-based mechanism for direct antimicrobial peptide activity against vaccinia virus membranes.

Antimicrobial peptides have activity against a wide variety of biological membranes and are an important component of innate immunity in vertebrate as well as invertebrate systems. The mechanisms of action of these peptides are incompletely understood and a number of competing but not necessarily mutually exclusive models exist. In this study we examined the virucidal activity of four peptides, the human cathelicidin derived LL37, Xenopus alanine-substituted Magainin-2 amide, uperin-3.1, and a cecropin-LL37 hybrid against vaccinia virus. The peptides were shown to be differentially virucidal but all were shown to attack the viral envelope, with LL37 being the most effective and uperin-3.1 the least. Density gradient analysis of the treated virions indicated the virus outer membrane was efficiently removed by peptide action and suggests a mechanism of direct virus inactivation that is consistent with the carpet model for peptide-mediated membrane disruption. Interestingly, the least effective peptide uperin-3.1 was equally effective as the others at inducing susceptibility to neutralizing antibody. This suggests that in addition to direct killing by a carpet-based mechanism, the peptides may simultaneously operate a different mechanism that exposes sequestered antigen without membrane removal.

Sleep in children with attention deficit/hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychological disorders in children. Sleep disturbances are also very prevalent among the pediatric age range and can lead to substantial behavioral and cognitive consequences that may mimic ADHD. Conversely, children with ADHD may suffer from significant sleep disturbances that may originate in the biochemical disturbances that underlie their deficits in executive function and attention. This review addresses both these issues and provides a concise yet timely assessment of the potential links between sleep disorders and ADHD.

Regulation of factor VIIIa by human activated protein C and protein S: inactivation of cofactor in the intrinsic factor Xase.

Factor VIIIa is a trimer of A1, A2, and A3-C1-C2 subunits. Inactivation of the cofactor by human activated protein C (APC) results from preferential cleavage at Arg336 within the A1 subunit, followed by cleavage at Arg562 bisecting the A2 subunit. In the presence of human protein S, the rate of APC-dependent factor VIIIa inactivation increased several-fold and correlated with an increased rate of cleavage at Arg562. (Active site-modified) factor IXa, blocked cleavage at the A2 site. However, APC-catalyzed inactivation of factor VIIIa proceeded at a similar rate independent of factor IXa, consistent with the location of the preferential cleavage site within the A1 subunit. Addition of protein S failed to increase the rate of cleavage at the A2 site when factor IXa was present. In the presence of factor X, cofactor inactivation was inhibited, due to a reduced rate of cleavage at Arg336. However, inclusion of protein S restored near original rates of factor VIIIa inactivation and cleavage at the A1 site, thus overcoming the factor X-dependent protective effect. These results suggest that in the human system, protein S stimulates APC-catalyzed factor VIIIa inactivation by facilitating cleavage of A2 subunit (an effect retarded in the presence of factor IXa), as well as abrogating protective interactions of the cofactor with factor X. (Blood. 2000;95:1714-1720)

Children of parents with mental illness. I: An overview from a nursing perspective.

This paper explores the psychosocial consequences of parental mental illness for child mental health and the implications for mental health nursing. The literature on risk and vulnerability to psychosocial disorder, resilience, child protection, disorder prevention and epidemiological data are reviewed. Based upon a health promotion approach, a model for mental health nursing advocacy for families of adult consumers is proposed as an effective means of preventing disorder in subsequent generations.

An investigation of factors that might influence the radiochemical purity and stability of 99mTc-MAG3.

Technetium 99m mercaptoacetyltriglycine (99mTc-MAG3) was prepared from a commercial kit by various techniques to assess the effect of a number of variables on radiochemical purity and stability. Its radiochemical purity was determined by high performance liquid chromatography at 0 and 6 h after preparation and was found to be consistently greater than 95%. It has been demonstrated that the radiochemical purity of 99mTc-MAG3 prepared according to the manufacturer's instructions is not influenced by the volume of 99mTc generator eluate used, agitation, the presence of air in the reaction vial or the use of a 99mTc generator eluate with a 99Tc:99mTc ratio of 16:1. A modified method of preparation in which the MAG3 kit is reconstituted with saline before addition of 99mTc-pertechnetate has been shown to yield a satisfactory product and should help to minimise the radiation dose to the fingers of radiopharmacy staff.

Localization of factor IXa and factor VIIIa interactive sites.

The contribution of the catalytic and noncatalytic domains of factor IXa to the interaction with its cofactor, factor VIIIa, was evaluated. Two proteolytic fragments of factor IXa, lacking some or all of the serine protease domain, failed to mimic the ability of factor IXa to enhance the reconstitution of factor VIIIa from isolated A1/A3-C1-C2 dimer and A2 subunit. Both fragments, however, inhibited this factor IXa-dependent activity. Selective thermal denaturation of the factor IXa serine protease domain eliminated its effect on factor VIIIa reconstitution. Modification of factor IXa with dansyl-Glu-Gly-Arg chloromethyl ketone (DEGR-IXa) stabilized this domain, and heat-treated DEGR-IXa retained its ability to enhance factor VIIIa reconstitution. These results indicate the importance of the serine protease domain as well as structures residing in the factor IXa light chain (gamma-carboxyglutamic acid and/or epidermal growth factor domains) for cofactor stabilizing activity. In the presence of phospholipid, the A1/A3-C1-C2 dimer produced a saturable increase in the fluorescence anisotropy of fluorescein-Phe-Phe-Arg chloromethyl ketone-modified factor IXa (Fl-FFR-IXa). This effect was inhibited by a factor IXa fragment comprised of the gamma-carboxyglutamic acid and epidermal growth factor domains. The difference in Fl-FFR-IXa anisotropy in the presence of A1/A3-C1-C2 dimer (delta r = 0.043) compared with factor VIIIa (delta r = 0.069) represented the contribution of the A2 subunit, A peptide corresponding to factor VIII A2 domain residues 558-565 decreased the factor VIIIa dependent-anisotropy of Fl-FFR-IXa to a value similar to that observed with the A1/A3-C1-C2 dimer. These results support a model of multiple interactive sites in the association of the enzyme-cofactor complex and localize sites for the A1/A3-C1-C2 dimer and the A2 subunit to the factor IXa light chain and serine protease domain, respectively.