Barriers and facilitators to smoking cessation within pregnant Aboriginal and/or Torres Strait Islander women: An integrative review.

OBJECTIVE: To synthesise primary research regarding the facilitators and barriers to smoking cessation amongst Aboriginal and/or Torres Strait Islander women during pregnancy. DESIGN: An integrative review. REVIEW METHODS: A systematic search of peer-reviewed literature from five databases published from January 2008 to April 2018. Articles were reviewed using the approach outlined by Whittemore and Knafl, with the identified themes collated and synthesised according to study characteristics and barriers and facilitators of smoking cessation. FINDINGS: Of the 310 papers retrieved, nine studies were included within the review (five quantitative and four qualitative). The quality of the studies were ascertained via Joanna Briggs Institute checklists for cross sectional analysis, randomized controlled trials, and qualitative research. The overall quality of the research was deemed acceptable. Two facilitators to smoking cessation within the studied population were identified: 'support to quit' and 'information and advice', while four barriers to smoking cessation within pregnant Aboriginal and/or Torres Strait Islander women were identified: 'smoking prevalence', 'high daily stress', 'ambivalence regarding adverse effects of smoking', and 'attitudes, knowledge and training of the healthcare professional'. CONCLUSIONS: Social and familial influences and daily stress have a strong impact on whether a woman feels she can quit smoking during pregnancy. However, in this study, information and advice regarding potential adverse effects of smoking on the foetus, or lack thereof, from health professionals either facilitated cessation of smoking in pregnancy or was a barrier to quitting. Likewise, a lack of awareness from midwives and doctors on smoking cessation strategies, such as nicotine replacement therapy, was a barrier for women. IMPLICATIONS FOR PRACTICE: The findings indicate that education regarding the adverse effects of smoking in pregnancy, as well as strategies on smoking cessation from midwives, doctors, and Aboriginal Health Workers within the antenatal period may have a positive effect on current smoking rates among pregnant Aboriginal and/or Torres Strait Islander women. Involving the partner/support person and family of the woman in this education may have a greater impact on smoking cessation rates through the woman gaining social and familial support in her decision to quit. Thus, healthcare workers require additional professional development to provide information and knowledge within a culturally competent manner. Successful smoking cessation programs for Aboriginal and Torres Strait Islander women during pregnancy could have measurable impacts on mortality rates for Indigenous infants and significantly contribute to 'Closing the Gap'.

Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis.

Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

Dsp rul: a spontaneous mouse mutation in desmoplakin as a model of Carvajal-Huerta syndrome.

Studies of spontaneous mutations in mice have provided valuable disease models and important insights into the mechanisms of human disease. Ruffled (rul) is a new autosomal recessive mutation causing abnormal hair coat in mice. The rul allele arose spontaneously in the RB156Bnr/EiJ inbred mouse strain. In addition to an abnormal coat texture, we found diffuse epidermal blistering, abnormal electrocardiograms (ECGs), and ventricular fibrosis in mutant animals. Using high-throughput sequencing (HTS) we found a frameshift mutation at 38,288,978bp of chromosome 13 in the desmoplakin gene (Dsp). The predicted mutant protein is truncated at the c-terminus and missing the majority of the plakin repeat domain. The phenotypes found in Dsp(rul) mice closely model a rare human disorder, Carvajal-Huerta syndrome. Carvajal-Huerta syndrome (CHS) is a rare cardiocutaneous disorder that presents in humans with wooly hair, palmoplantar keratoderma and ventricular cardiomyopathy. CHS results from an autosomal recessive mutation on the 3' end of desmoplakin (DSP) truncating the full length protein. The Dsp(rul) mouse provides a new model to investigate the pathogenesis of CHS, as well as the underlying basic biology of the adhesion molecules coded by the desmosomal genes.

Contrasting alterations to synaptic and intrinsic properties in upper-cervical superficial dorsal horn neurons following acute neck muscle inflammation.

BACKGROUND: Acute and chronic pain in axial structures, like the back and neck, are difficult to treat, and have incidence as high as 15%. Surprisingly, most preclinical work on pain mechanisms focuses on cutaneous structures in the limbs and animal models of axial pain are not widely available. Accordingly, we developed a mouse model of acute cervical muscle inflammation and assessed the functional properties of superficial dorsal horn (SDH) neurons. RESULTS: Male C57/Bl6 mice (P24-P40) were deeply anaesthetised (urethane 2.2 g/kg i.p) and the rectus capitis major muscle (RCM) injected with 40 µl of 2% carrageenan. Sham animals received vehicle injection and controls remained anaesthetised for 2 hrs. Mice in each group were sacrificed at 2 hrs for analysis. c-Fos staining was used to determine the location of activated neurons. c-Fos labelling in carrageenan-injected mice was concentrated within ipsilateral (87% and 63% of labelled neurons in C1 and C2 segments, respectively) and contralateral laminae I - II with some expression in lateral lamina V. c-Fos expression remained below detectable levels in control and sham animals. In additional experiments, whole cell recordings were obtained from visualised SDH neurons in transverse slices in the ipsilateral C1 and C2 spinal segments. Resting membrane potential and input resistance were not altered. Mean spontaneous EPSC amplitude was reduced by ~20% in neurons from carrageenan-injected mice versus control and sham animals (20.63 ± 1.05 vs. 24.64 ± 0.91 and 25.87 ± 1.32 pA, respectively). The amplitude (238 ± 33 vs. 494 ± 96 and 593 ± 167 pA) and inactivation time constant (12.9 ± 1.5 vs. 22.1 ± 3.6 and 15.3 ± 1.4 ms) of the rapid A type potassium current (IAr), the dominant subthreshold current in SDH neurons, were reduced in carrageenan-injected mice. CONCLUSIONS: Excitatory synaptic drive onto, and important intrinsic properties (i.e., IAr) within SDH neurons are reduced two hours after acute muscle inflammation. We propose this time point represents an important transition period between peripheral and central sensitisation with reduced excitatory drive providing an initial neuroprotective mechanism during the early stages of the progression towards central sensitisation.

Hearing impairment in hypothyroid dwarf mice caused by mutations of the thyroid peroxidase gene.

Thyroid hormone (TH) is essential for proper cochlear development and function, and TH deficiencies cause variable hearing impairment in humans and mice. Thyroid peroxidase (TPO) catalyzes key reactions in TH synthesis, and TPO mutations have been found to underlie many cases of congenital hypothyroidism in human patients. In contrast, only a single mutation of the mouse TPO gene has been reported previously (Tpo(R479C)) but was not evaluated for auditory function. Here, we describe and characterize two new mouse mutations of Tpo with an emphasis on their associated auditory deficits. Mice homozygous for these recessive mutations have dysplastic thyroid glands and lack detectable levels of TH. Because of the small size of mutant mice, the mutations were named teeny (symbol Tpo(tee)) and teeny-2 Jackson (Tpo(tee-2J)). Tpo(tee) is a single base-pair missense mutation that was induced by ENU, and Tpo(tee-2J) is a 64 bp intragenic deletion that arose spontaneously. The Tpo(tee) mutation changes the codon for a highly conserved tyrosine to asparagine (p.Y614N), and the Tpo(tee-2J) mutation deletes a splice donor site, which results in exon skipping and aberrant transcripts. Mutant mice are profoundly hearing impaired with auditory brainstem response (ABR) thresholds about 60 dB above those of non-mutant controls. The maturation of cochlear structures is delayed in mutant mice and tectorial membranes are abnormally thick. To evaluate the effect of genetic background on auditory phenotype, we produced a C3.B6-Tpo(tee-2J) congenic strain and found that ABR thresholds of mutant mice on the C3H/HeJ strain background are 10-12 dB lower than those of mutant mice on the C57BL/6 J background. The Tpo mutant strains described here provide new heritable mouse models of congenital hypothyroidism that will be valuable for future studies of thyroid hormones' role in auditory development and function.

The mouse mutation "thrombocytopenia and cardiomyopathy" (trac) disrupts Abcg5: a spontaneous single gene model for human hereditary phytosterolemia/sitosterolemia.

The spontaneous mouse mutation "thrombocytopenia and cardiomyopathy" (trac) causes macrothrombocytopenia, prolonged bleeding times, anemia, leukopenia, infertility, cardiomyopathy, and shortened life span. Homozygotes show a 20-fold decrease in platelet numbers and a 3-fold increase in platelet size with structural alterations and functional impairments in activation and aggregation. Megakaryocytes in trac/trac mice are present in increased numbers, have poorly developed demarcation membrane systems, and have decreased polyploidy. The thrombocytopenia is not intrinsic to defects at the level of hematopoietic progenitor cells but is associated with a microenvironmental abnormality. The trac mutation maps to mouse chromosome 17, syntenic with human chromosome 2p21-22. A G to A mutation in exon 10 of the adenosine triphosphate (ATP)-binding cassette subfamily G, member 5 (Abcg5) gene, alters a tryptophan codon (UGG) to a premature stop codon (UAG). Crosses with mice doubly transgenic for the human ABCG5 and ABCG8 genes rescued platelet counts and volumes. ABCG5 and ABCG8 form a functional complex that limits dietary phytosterol accumulation. Phytosterolemia in trac/trac mice confirmed a functional defect in the ABCG5/ABCG8 transport system. The trac mutation provides a new clinically significant animal model for human phytosterolemia and provides a new means for studying the role of phytosterols in hematologic diseases and testing therapeutic interventions.

Notch signalling in the paraxial mesoderm is most sensitive to reduced Pofut1 levels during early mouse development.

BACKGROUND: The evolutionarily conserved Notch signalling pathway regulates multiple developmental processes in a wide variety of organisms. One critical posttranslational modification of Notch for its function in vivo is the addition of O-linked fucose residues by protein O-fucosyltransferase 1 (POFUT1). In addition, POFUT1 acts as a chaperone and is required for Notch trafficking. Mouse embryos lacking POFUT1 function die with a phenotype indicative of global inactivation of Notch signalling. O-linked fucose residues on Notch can serve as substrates for further sugar modification by Fringe (FNG) proteins. Notch modification by Fringe differently affects the ability of ligands to activate Notch receptors in a context-dependent manner indicating a complex modulation of Notch activity by differential glycosylation. Whether the context-dependent effects of Notch receptor glycosylation by FNG reflect different requirements of distinct developmental processes for O-fucosylation by POFUT1 is unclear. RESULTS: We have identified and characterized a spontaneous mutation in the mouse Pofut1 gene, referred to as "compact axial skeleton" (cax). Cax carries an insertion of an intracisternal A particle retrotransposon into the fourth intron of the Pofut1 gene and represents a hypomorphic Pofut1 allele that reduces transcription and leads to reduced Notch signalling. Cax mutant embryos have somites of variable size, showed partly abnormal Lfng expression and, consistently defective anterior-posterior somite patterning and axial skeleton development but had virtually no defects in several other Notch-regulated early developmental processes outside the paraxial mesoderm that we analyzed. CONCLUSION: Notch-dependent processes apparently differ with respect to their requirement for levels of POFUT1. Normal Lfng expression and anterior-posterior somite patterning is highly sensitive to reduced POFUT1 levels in early mammalian embryos, whereas other early Notch-dependent processes such as establishment of left-right asymmetry or neurogenesis are not. Thus, it appears that in the presomitic mesoderm (PSM) Notch signalling is particularly sensitive to POFUT1 levels. Reduced POFUT1 levels might affect Notch trafficking or overall O-fucosylation. Alternatively, reduced O-fucosylation might preferentially affect sites that are substrates for LFNG and thus important for somite formation and patterning.

Caracterización molecular y detecciónde betalactamasas de espectro extendido en cepas de E. coli y K. pneumoniae aisladas en las unidades de cuidados intensivos de un Hospital Universitario / Molecular characterization and extended spectrum betalactamase detection in E. coli and K. pneumoniae strains isolates from intensive care units in a Teaching Hospital

La producción de Betalactamasas de Espectro Extendido por cepas de E. coli y K. pneumoniae, es un grave problema de salud pública ya que causa la pérdida de la eficacia terapéutica a los antibióticos ß-lactámicos. En este trabajo se investigó la presencia de betalactamasas de espectro extendido en cepas de E. coli y K. pneumoniae aisladas de pacientes de las unidades de cuidados intensivos de un hospital universitario. Se estudiaron 41 cepas de E. coli y 59 de K. pneumoniae, aisladas de los cultivos bacteriológicos realizados en el Centro de Referencia Bacterológica del Sevicio Autónomo Hospital Universitario de Maracaibo (SAHUM). Para la detección de betalactamasas de espectro extendido se utilizaron los métodos normalizados por el Clinical and Laboratory Standards Institute (CLSI). El 39,02% de las cepas de E. coli y el 52,54% de las de K. pneumoniae fueron betalactamasas de espectro extendido positivas, en estas cepas se observó resistencia acompañante a quinolonas, aminoglicósidos, cloranfenicol, tetraciclina y trimetoprima/sulfametoxazol. El estudio epidemiológico mediante Electroforesis de Campo Pulsado, mostró una gran diversidad genética entre los aislamientos, esta policlonalidad indica que la diseminación dentro del ambiente hospitalario no se da por transmisión de una cepa entre pacientes, sino que se da por transferencia de plásmidos entre diferentes cepas producto de la alta presión selectiva ejercida por la mala utilización de cefalosporinas de tercera generació.

Especies de Aeromonas en vegetales frescos que se expenden en un mercado popular de Maracaibo / Aeromonas species in fresh vegetables that are expended in a popular market of Maracaibo

Las especies de Aeromonas son patógenos emergentes que se pueden recuperar de una gran variedad de alimentos. El objetivo de esta investigación fue determinar la frecuencia de Aeromonas spp. en vegetales frescos que se expenden en Maracaibo. Se analizaron 150 muestras: 50 lechuga, 50 cilantro y 50 perejil. Para el aislamiento se utilizó agua peptonada alcalina (medio de enriquecimiento), agar almidón ampicilina y DNasa-azul de toluidina-ampilcilina agar (medios selectivos). La identificación se realizó empleando pruebas bio-químicas. La frecuencia de Aeromonas spp. fue de 37 (24,67 por ciento), siendo las muestras de cilantro las que presentaron el mayor número de aislamiento 24 (52,00 por ciento). A. caviae fue la especie mas recuperada 27 (72,97 por ciento), seguida de A. hydrophila 10 (27,03 por ciento). Estos resultados evidencian que los vegetales analizados presentan elevados niveles de contaminación por Aeromonas, lo cual indica que se deben tomar medidas para minimizar los riesgos microbiológicos que representan estos alimentos para los consumidores.

The netrin 1 receptors Unc5h3 and Dcc are necessary at multiple choice points for the guidance of corticospinal tract axons.

Migrating axons require the correct presentation of guidance molecules, often at multiple choice points, to find their target. Netrin 1, a bifunctional cue involved in both attracting and repelling axons, is involved in many cell migration and axon pathfinding processes in the CNS. The netrin 1 receptor DCC and its Caenorhabditis elegans homolog UNC-40 have been implicated in directing the guidance of axons toward netrin sources, whereas the C. elegans UNC-6 receptor, UNC-5 is necessary for migrations away from UNC-6. However, a role of vertebrate UNC-5 homologs in axonal migration has not been demonstrated. We demonstrate that the Unc5h3 gene product, shown previously to regulate cerebellar granule cell migrations, also controls the guidance of the corticospinal tract, the major tract responsible for coordination of limb movements. Furthermore, we show that corticospinal tract fibers respond differently to loss of UNC5H3. In addition, we observe corticospinal tract defects in mice homozygous for a spontaneous mutation that truncates the Dcc transcript. Postnatal day 0 netrin 1 mutant mice also demonstrate corticospinal tract abnormalities. Last, interactions between the Dcc and Unc5h3 mutations were observed in gene dosage experiments. This is the first evidence of an involvement in axon guidance for any member of the vertebrate unc-5 family and confirms that both the cellular and axonal guidance functions of C. elegans unc-5 have been conserved in vertebrates.