Contribution of Stretch to the Change of Activation Properties of Muscle Fibers in the Diaphragm at the Transition from Fetal to Neonatal Life

The transition from fetal to postnatal life involves clearance of liquid from the lung and airways, and rapid formation of a functional residual capacity. Despite the importance of the diaphragm in this process, the impact of birth on the mechanical and functional activity of its muscle fibers is not known. This study determined the contractile characteristics of individual “skinned” diaphragm fibers from 70 days (0.47) gestation to after birth in sheep. Based on differential sensitivity to the divalent ions calcium (Ca2+) and strontium (Sr2+), all fibers in the fetal diaphragm were classified as “fast,” whereas fibers from the adult sheep diaphragm exhibited a “hybrid” phenotype where both “fast” and “slow” characteristics were present within each single fiber. Transition to the hybrid phenotype occurred at birth, was evident after only 40 min of spontaneous breathing, and could be induced by simple mechanical stretch of diaphragm fibers from near-term fetuses (∼147 days gestation). Both physical stretch of isolated fibers, and mechanical ventilation of the fetal diaphragm in situ, significantly increased sensitivity to Ca2+ and Sr2+, maximum force generating capacity, and decreased passive tension in near-term and preterm fetuses; however, only fibers from near-term fetuses showed a complete transition to a “hybrid” activation profile. These findings suggest that stretch associated with the transition from a liquid to air-filled lung at birth induces physical changes of proteins determining the activation and elastic properties of the diaphragm. These changes may allow the diaphragm to meet the increased mechanical demands of breathing immediately after birth

Knowledge Gaps in the Fetal to Neonatal Transition of Infants With a Congenital Diaphragmatic Hernia

Clinical research for infants born with a congenital diaphragmatic hernia (CDH) has until recently mainly focused on advances in prenatal and postnatal treatment. However, during the early perinatal transition period there are major physiological adaptations. For most infants these changes will happen uneventfully, but for CDH infants this marks the beginning of serious respiratory complications. In recent years, there is emerging evidence that the clinical management during the perinatal stabilization period in the delivery room may influence postnatal outcomes. Herein, we discuss major knowledge gaps and novel concepts that aim to optimize fetal to neonatal transition for infants with CDH. One such novel and interesting approach is performing resuscitation with an intact umbilical cord, the efficacy of this procedure is currently being investigated in several clinical trials. Furthermore, close evaluation of neonatal physiological parameters in the first 24 h of life might provide early clues concerning the severity of lung hypoplasia and the risk of adverse outcomes. We will provide an overview of trending concepts and discuss potential areas for future research

Increasing Respiratory Effort With 100% Oxygen During Resuscitation of Preterm Rabbits at Birth

Background: Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O2 may reduce the risk of hypoxia and increase respiratory effort at birth. Methods: Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% (n = 12) or 100% O2 (n = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O2 in kittens who started in 21% O2, and remained at 100% O2 for kittens who started the experiment in 100% O2. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Results: Initially, kittens receiving 21% O2 had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O2 [median (IQR) respiratory rate: 16 (4–28) vs. 38 (29–46) bpm, p = 0.001; variability in inter-breath interval: 33.3% (17.2–50.1%) vs. 27.5% (18.6–36.3%), p = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O2 (11/12 vs. 1/8, p = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O2. FRC was not different between study groups at both timepoints. Conclusion: Initiating resuscitation with 100% O2 resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are mandatory to confirm the benefit of this approach in terms of oxygenation. In addition, the ability to avoid hyperoxia after initiation of resuscitation with 100% oxygen, using a titration protocol based on oxygen saturation, needs to be clarified

Sheep Updates 2005 - Part 5

This session covers eleven papers from different authors; MARKET INFORMATION 1. Crystal Spring - Crystal clear and consistant, Geoff Duddy, Livestock Officer (Sheep & Wool) Yanco, NSW, Brent McLoud, (Product Development Officer) Cowra, NSW, John Sullivan, J.J Dresser and Co (Agent), Woodstock, NSW 2. An overview of Recent Developments in Dark and Medullated Fibre Testing, T.J. Mahar, A. Balasingam, AWTA Ltd 3. Opportunities and Implications for Wool Producers of the TEAM3 Prediction Equations, J.H. Stanton12 K.M.S. Curtis1 , 1Department of Agriculture Western Australia, 2 Curtin University, WA 4. Premiums and Discounts for Fibre Properties in Superfine Wool, Now and in the Future?, K.M.S. Curtis1, P.R. Lamb2, 1 Department of Agriculture Western Australia, 2Lambshift Consulting, Geelong VIC FEEDLOTTING 5. Manure in sheep feedlots: problem or opportunity?, Eliza Dowling, Ned Crossley Department of Agriculture , Western Australia, Surrender Mann, Chemistry Centre (WA), East Perth WA, 6. The State of Lamb Confinement Feeding in WA, Ned Crossley, Department of Agriculture, Western Australia 7. Finishing lambs in a feed lot - Is it profitable?, Lucy Anderton, Department of Agriculture, Western Australia 8. Repeated live weights can mardinally improve prediction of compliance to markey specifications, Mattew Kelly, Andrew Swan, CSIRO livestock industries, Ian McFarland, Department of Agriculture Western Australia. WELFARE 9. Mulesing accreditation - to be or not to be? Di Evans, Department of Agriculture, Western Australia. 10. The Economic and Research Implications of managing Merino Sheep with out Mulesing, K. Bell, Sheep Management and Production Consultants, North Fremantle WA, D. Sackett, Homes Sackett and Associates, Wagga Wagga NSW 11. How do lambs fare during curfew, Dr Robin Jacob, Department of Agriculture, Western Australi

Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC):study protocol for a multicentre, randomised controlled trial

Introduction Pulmonary hypertension is a majordeterminant of postnatal survival in infants with acongenital diaphragmatic hernia (CDH). The current careduring the perinatal stabilisation period in these infantsmight contribute to the development of pulmonaryhypertension after birth—in particular umbilical cordclamping before lung aeration. An ovine model ofdiaphragmatic hernia demonstrated that cord clampingafter lung aeration, called physiological-based cordclamping (PBCC), avoided the initial high pressures in thelung vasculature while maintaining adequate blood flow,thereby avoiding vascular remodelling and aggravationof pulmonary hypertension. We aim to investigate if theimplementation of PBCC in the perinatal stabilisation periodof infants born with a CDH could reduce the incidence ofpulmonary hypertension in the first 24 hours after birth.Methods and analysis We will perform a multicentre,randomised controlled trial in infants with an isolatedleft-sided CDH, born at ≥35.0 weeks. Before birth, infantswill be randomised to either PBCC or immediate cordclamping, stratified by treatment centre and severity ofpulmonary hypoplasia on antenatal ultrasound. PBCCwill be performed using a purpose- built resuscitationtrolley. Cord clamping will be performed when the infantis considered respiratory stable, defined as a heartrate >100 bpm, preductal oxygen saturation >85%,while using a fraction of inspired oxygen of <0.5. Theprimary outcome is pulmonary hypertension diagnosedin the first 24 hours after birth, based on clinical andechocardiographic parameters. Secondary outcomesinclude neonatal as well as maternal outcomes.Ethics and dissemination Central ethical approvalwas obtained from the Medical Ethical Committee ofthe Erasmus MC, Rotterdam, The Netherlands (METC2019-0414). Local ethical approval will be obtained bysubmitting the protocol to the regulatory bodies and localinstitutional review boards

“When will this end? Will it end?” The impact of the March-June 2020 UK Covid-19 lockdown response on mental health : a longitudinal survey of mothers in the Born in Bradford study

OBJECTIVES: To explore clinically important increases in depression/anxiety from before to during the first UK COVID-19 lockdown and factors related to this change, with a particular focus on ethnic differences. DESIGN: Pre-COVID-19 and lockdown surveys nested within two longitudinal Born in Bradford cohort studies. PARTICIPANTS: 1860 mothers with a child aged 0–5 or 9–13, 48% Pakistani heritage. MAIN OUTCOME MEASURES: ORs for a clinically important increase (5 points or more) in depression (eight item Patient Health Questionnaire (PHQ-8)) and anxiety (Generalised Anxiety Disorder Assessment (GAD-7)) in unadjusted regression analyses, repeated with exposures of interest separated by ethnicity to look for differences in magnitude of associations, and lived experience of mothers captured in open text questions. RESULTS: The number of women reporting clinically important depression/anxiety increased from 11% to 20% (95% CI 10%–13%; 18%–22%) and from 10% to 16% (95% CI 8%–11%; 15%–18%), respectively. Increases in depression/anxiety were associated with loneliness (OR=8.37, 95% CI 5.70 to 12.27; 8.50, 95% CI 5.71 to 12.65, respectively); financial (6.23, 95% CI 3.96 to 9.80; 6.03, 95% CI 3.82 to 9.51), food (3.33, 95% CI 2.09 to 5.28; 3.46, 95% CI 2.15 to 5.58) and housing insecurity (3.29, 95% CI 2.36 to 4.58; 3.0, 95% CI 2.11 to 4.25); a lack of physical activity (3.13, 95% CI 2.15 to 4.56; 2.55, 95% CI 1.72 to 3.78); and a poor partner relationship (3.6, 95% CI 2.44 to 5.43; 5.1, 95% CI 3.37 to 7.62). The magnitude of associations between key exposures and worsening mental health varied between ethnic groups. Responses to open text questions illustrated a complex interplay of challenges contributing to mental ill health including: acute health anxieties; the mental load of managing multiple responsibilities; loss of social support and coping strategies; pressures of financial and employment insecurity; and being unable to switch off from the pandemic. CONCLUSIONS: Mental ill health has worsened for many during the COVID-19 lockdown, particularly in those who are lonely and economically insecure. The magnitude of associations between key exposures and worsening mental health varied between ethnic groups. Mental health problems may have longer term consequences for public health and interventions that address the potential causes are needed

Length and Velocity Formulas in Approximate Oscillator-Strength Calculations

The matrix element for electric dipole transitions is correctly given by the length formula in the Hartree-Fock, configuration-interaction, and related approximations, which involve the diagonalization of an approximate, but nonlocal, Hamiltonian

Predicting intention to treat HIV-infected patients among Tanzanian and Sudanese medical and dental students using the theory of planned behaviour - a cross sectional study

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic poses significant challenges to the low income countries in sub Saharan Africa (SSA), affecting the attrition rate among health care workers, their level of motivation, and absenteeism from work. Little is known about how to deal with deterioration of human resources in the health care systems. This study aimed to predict the intention to provide surgical treatment to HIV infected patients among medical- and dental students in Tanzania and Sudan using an extended version of the Theory of Planned Behaviour (TPB).</p> <p>Methods</p> <p>Four hundred and seventy five medical- and dental students at the University of Dar es Salaam (mean age, 25 yr) and 642 dental students attending 6 public and private dental faculties in Khartoum (mean age 21.7 yr) completed self-administered TPB questionnaires in 2005 and 2007, respectively.</p> <p>Results</p> <p>Both Tanzanian and Sudanese students demonstrated strong intentions to provide care for people with HIV and AIDS. Stepwise linear regression revealed that the TPB accounted for 51% (43% in Tanzania and Sudan) of the variance in intention across study sites. After having controlled for country and past behaviour, the TPB in terms of attitudes, subjective norms and perceived behavioural control accounted for 34% and moral norms for an additional 2,3% of the explainable variance in intention. Across both study sites, attitudes were the strongest predictor of intention followed in descending order by subjective norms, moral norms and perceived behavioural control.</p> <p>Conclusion</p> <p>The TPB is applicable to students' care delivery intentions in the context of HIV and AIDS across the two SSA countries investigated. It is suggested that attitudes, subjective norms, moral norms and perceived behavioural control are key factors in students' willingness to treat AIDS and HIV infected patients and should be targets of interventions aimed at improving the quality of health care delivery in this context.</p

In vivo and in silico determination of essential genes of Campylobacter jejuni

<p>Abstract</p> <p>Background</p> <p>In the United Kingdom, the thermophilic <it>Campylobacter </it>species <it>C. jejuni </it>and <it>C. coli </it>are the most frequent causes of food-borne gastroenteritis in humans. While campylobacteriosis is usually a relatively mild infection, it has a significant public health and economic impact, and possible complications include reactive arthritis and the autoimmune diseases Guillain-Barré syndrome. The rapid developments in "omics" technologies have resulted in the availability of diverse datasets allowing predictions of metabolism and physiology of pathogenic micro-organisms. When combined, these datasets may allow for the identification of potential weaknesses that can be used for development of new antimicrobials to reduce or eliminate <it>C. jejuni </it>and <it>C. coli </it>from the food chain.</p> <p>Results</p> <p>A metabolic model of <it>C. jejuni </it>was constructed using the annotation of the NCTC 11168 genome sequence, a published model of the related bacterium <it>Helicobacter pylori</it>, and extensive literature mining. Using this model, we have used <it>in silico </it>Flux Balance Analysis (FBA) to determine key metabolic routes that are essential for generating energy and biomass, thus creating a list of genes potentially essential for growth under laboratory conditions. To complement this <it>in silico </it>approach, candidate essential genes have been determined using a whole genome transposon mutagenesis method. FBA and transposon mutagenesis (both this study and a published study) predict a similar number of essential genes (around 200). The analysis of the intersection between the three approaches highlights the shikimate pathway where genes are predicted to be essential by one or more method, and tend to be network hubs, based on a previously published <it>Campylobacter </it>protein-protein interaction network, and could therefore be targets for novel antimicrobial therapy.</p> <p>Conclusions</p> <p>We have constructed the first curated metabolic model for the food-borne pathogen <it>Campylobacter jejuni </it>and have presented the resulting metabolic insights. We have shown that the combination of <it>in silico </it>and <it>in vivo </it>approaches could point to non-redundant, indispensable genes associated with the well characterised shikimate pathway, and also genes of unknown function specific to <it>C. jejuni</it>, which are all potential novel <it>Campylobacter </it>intervention targets.</p