The relationship between klotho, testosterone, and sexual health parameters among US adult men.

BACKGROUND: Klotho is a pleotropic hormone involved in a multitude of biological processes necessary for healthy aging, and affords protection from adverse events such as cardiovascular disease, inflammation, and various cancers. Emerging evidence suggests that klotho is also an important component of biochemical pathways that regulate hormone balance, which may include those pathways governing testosterone production and men's sexual health, though data are limited and results are mixed. OBJECTIVE: Using a cohort of 767 men from the NHANES 2015-2016 survey cycle, we set out to quantify the association between serum klotho levels and serum testosterone levels, as well as clinical markers of men's sexual health (e.g., testosterone:estrogen ratio, bioavailable testosterone, and free testosterone). METHODS: Multivariable linear and logistic regression models while controlling for potential confounders were constructed to quantify the relationship between serum klotho and testosterone, as well as between serum klotho and odds of low testosterone (serum testosterone < 300 ng/dL). RESULTS: A positive association was observed between serum klotho and testosterone (ß = 0.18, p = 0.04). Serum klotho levels were also stratified into quartiles, and we observed statistically significant increases in testosterone for increasing quartile level of klotho using the first quartile as the reference group (ß = 90.51, p = 0.001, ß = 106.93, p = 0.002, ß = 95.33, p = 0.03 for quartiles 2, 3, and 4, respectively). The average testosterone values by quartiles of klotho were 306.9 ng/dL, 390 ng/dL, 409.3 ng/dL, and 436.6 ng/dL, respectively. We modeled important proxies for sexual health including bioavailable and free testosterone, the testosterone:estradiol ratio, and C-reactive protein. Men in the second quartile of klotho had a significantly lower odds of an abnormal testosterone:estradiol ratio compared to the first quartile [OR = 0.18, 95% CI = (0.03, 0.98)].We observed null associations between continuous serum klotho and odds of low testosterone [OR = 1.0, 95% CI = (1.0, 1.0)], and when stratified by quartile, we observed a significant decrease in the odds of low testosterone for individuals in the second quartile of klotho compared to the first quartile [OR = 0.21, 95% CI = (0.05, 0.91)]. In addition, C-reactive protein was inversely associated with testosterone in men (ß = - 4.65, p = 0.001), and inversely associated with quartiles of klotho (ß = - 2.28, p = 0.04, ß = - 2.22, p = 0.04, ß = - 2.28, p = 0.03, for quartiles 2, 3, and 4, respectively). CONCLUSION: Our findings support previous studies suggesting a role for klotho in testosterone levels and sexual function among men. Future studies are warranted to corroborate these findings, determine clinical significance, and elucidate potential mechanisms underlying these associations.

Adolescent Binge Drinking Is Associated With Accelerated Decline of Gray Matter Volume.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan-Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose-response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

New guidelines for research in airway device evaluation: time for an updated approach (ADEPT-2) to the Difficult Airway Society's 'ADEPT' strategy?

In this article we present the learning from a clinical study of airway device evaluation, conducted under the framework of the Difficult Airway Society (DAS, UK) 'ADEPT' (airway device evaluation project team) strategy. We recommend a change in emphasis from small scale randomised controlled trials conducted as research, to larger-scale observational, post-marketing evaluation audits as a way of obtaining more meaningful information.

Assessing a novel second generation laryngeal mask airway using the 'ADEPT' approach: results from the LMA® Protector™ observational study.

To address the problem of lack of clinical evidence for airway devices introduced to the market, the Difficult Airway Society (UK) developed an approach (termed ADEPT; Airway Device Evaluation Project Team) to standardise the model for device evaluation. Under this framework we assessed the LMA Protector, a second generation laryngeal mask airway. A total of 111 sequential adult patients were recruited and the LMA Protector inserted after induction of general anaesthesia. Effective insertion was confirmed by resistance to further distal movement, manual ventilation, and listening for gas leakage at the mouth. The breathing circuit was connected to the airway channel and airway patency confirmed with manual test ventilation at 20 cm H20 (water) pressure for 3 s. Data was collected in relation to the time for placement, intraoperative performance and postoperative performance of the airway device. Additionally, investigators rated the ease of insertion and adequacy of lung ventilation on a 5-point scale. The median (interquartile range [range]) time taken to insertion of the device was 31 (26-40[14-780]) s with the ability to ventilate after device insertion 100 (95% CI 96.7- 100)%. Secondary endpoints included one or more manoeuvres 60.3 (95% CI 50.6-69.5)% cases requiring to assist insertion; a median ease of insertion score of 4 (2-5[3-5]), and a median adequacy of ventilation score of 5 (5-5[4-5]). However, the first time insertion rate failure was 9.9% (95% CI 5.1-17.0%). There were no episodes of patient harm recorded, particularly desaturation. The LMA Protector appears suitable for clinical use, but an accompanying article discusses our reflections on the ADEPT approach to studying airway devices from a strategic perspective.

Preventing unrecognised oesophageal intubation: a consensus guideline from the Project for Universal Management of Airways and international airway societies.

Across multiple disciplines undertaking airway management globally, preventable episodes of unrecognised oesophageal intubation result in profound hypoxaemia, brain injury and death. These events occur in the hands of both inexperienced and experienced practitioners. Current evidence shows that unrecognised oesophageal intubation occurs sufficiently frequently to be a major concern and to merit a co-ordinated approach to address it. Harm from unrecognised oesophageal intubation is avoidable through reducing the rate of oesophageal intubation, combined with prompt detection and immediate action when it occurs. The detection of 'sustained exhaled carbon dioxide' using waveform capnography is the mainstay for excluding oesophageal placement of an intended tracheal tube. Tube removal should be the default response when sustained exhaled carbon dioxide cannot be detected. If default tube removal is considered dangerous, urgent exclusion of oesophageal intubation using valid alternative techniques is indicated, in parallel with evaluation of other causes of inability to detect carbon dioxide. The tube should be removed if timely restoration of sustained exhaled carbon dioxide cannot be achieved. In addition to technical interventions, strategies are required to address cognitive biases and the deterioration of individual and team performance in stressful situations, to which all practitioners are vulnerable. These guidelines provide recommendations for preventing unrecognised oesophageal intubation that are relevant to all airway practitioners independent of geography, clinical location, discipline or patient type.

Airway management guidance for the endemic phase of COVID-19.

It is now apparent that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) will remain endemic for some time. Improved therapeutics and a vaccine may shorten this period, but both are far from certain. Plans must be put in place on the assumption that the virus and its disease will continue to affect the care of patients and the safety of staff. This will impact particularly on airway management due to the inherent risk to staff during such procedures. Research is needed to clarify the nature and risk of respiratory aerosol-generating procedures. Improved knowledge of the dynamics of SARS-CoV-2 infection and immunity is also required. In the meantime, we describe the current status of airway management during the endemic phase of the COVID-19 pandemic. Some controversies remain unresolved, but the safety of patients and staff remains paramount. Current evidence does not support or necessitate dramatic changes to choices for anaesthetic airway management. Theatre efficiency and training issues are a challenge that must be addressed, and new information may enable this.

An Irish National Diabetes in Pregnancy Audit: aiming for best outcomes for women with diabetes.

AIMS: The purpose of this study was to identify the number of pregnancies affected by pre-gestational diabetes in the Republic of Ireland; to report on pregnancy outcomes and to identify areas for improvement in care delivery and clinical outcomes. METHODS: Healthcare professionals caring for women with pre-gestational diabetes during pregnancy were invited to participate in this retrospective study. Data pertaining to 185 pregnancies in women attending 15 antenatal centres nationally were collected and analysed. Included pregnancies had an estimated date of delivery between 1 January and 31 December 2015. RESULTS: The cohort consisted of 122 (65.9%) women with Type 1 diabetes and 56 (30.3%) women with Type 2 diabetes. The remaining 7 (3.8%) pregnancies were to women with maturity-onset diabetes of the young (MODY) (n = 6) and post-transplant diabetes (n = 1). Overall women were poorly prepared for pregnancy and lapses in specific areas of service delivery including pre-pregnancy care and retinal screening were identified. The majority of pregnancies 156 (84.3%) resulted in a live birth. A total of 103 (65.5%) women had a caesarean delivery and 58 (36.9%) infants were large for gestational age. CONCLUSIONS: This audit identifies clear areas for improvement in delivery of care for women with diabetes in the Republic of Ireland before and during pregnancy.

The high prevalence and impact of rheumatic heart disease in pregnancy in First Nations populations in a high-income setting: a prospective cohort study.

OBJECTIVE: To describe the epidemiology of rheumatic heart disease (RHD) in pregnancy in Australia and New Zealand (A&NZ). DESIGN: Prospective population-based study. SETTING: Hospital-based maternity units throughout A&NZ. POPULATION: Pregnant women with RHD with a birth outcome of ≥20 weeks of gestation between January 2013 and December 2014. METHODS: We identified eligible women using the Australasian Maternity Outcomes Surveillance System (AMOSS). De-identified antenatal, perinatal and postnatal data were collected and analysed. MAIN OUTCOME MEASURES: Prevalence of RHD in pregnancy. Perinatal morbidity and mortality. RESULTS: There were 311 pregnancies associated with women with RHD (4.3/10 000 women giving birth, 95% CI 3.9-4.8). In Australia, 78% were Aboriginal or Torres Strait Islander (60.4/10 000, 95% CI 50.7-70.0), while in New Zealand 90% were Maori or Pasifika (27.2/10 000, 95% CI 22.0-32.3). One woman (0.3%) died and one in ten was admitted to coronary or intensive care units postpartum. There were 314 births with seven stillbirths (22.3/1000 births) and two neonatal deaths (6.5/1000 births). Sixty-six (21%) live-born babies were preterm and one in three was admitted to neonatal intensive care or special care units. CONCLUSION: Rheumatic heart disease in pregnancy persists in disadvantaged First Nations populations in A&NZ. It is associated with significant cardiac and perinatal morbidity. Preconception planning and counselling and RHD screening in at-risk pregnant women are essential for good maternal and baby outcomes. TWEETABLE ABSTRACT: Rheumatic heart disease in pregnancy persists in First Nations people in Australia and New Zealand and is associated with major cardiac and perinatal morbidity.

Incarcerated aboriginal women's experiences of accessing healthcare and the limitations of the 'equal treatment' principle.

BACKGROUND: Colonization continues in Australia, sustained through institutional and systemic racism. Targeted discrimination and intergenerational trauma have undermined the health and wellbeing of Australia's Aboriginal and Torres Strait Islander population, leading to significantly poorer health status, social impoverishment and inequity resulting in the over-representation of Aboriginal people in Australian prisons. Despite adoption of the 'equal treatment' principle, on entering prison in Australia entitlements to the national universal healthcare system are revoked and Aboriginal people lose access to health services modelled on Aboriginal concepts of culturally safe healthcare available in the community. Incarcerated Aboriginal women experience poorer health outcomes than incarcerated non-Indigenous women and Aboriginal men, yet little is known about their experiences of accessing healthcare. We report the findings of the largest qualitative study with incarcerated Aboriginal women in New South Wales (NSW) Australia in over 15 years. METHODS: We employed a decolonizing research methodology, 'community collaborative participatory action research', involving consultation with Aboriginal communities prior to the study and establishment of a Project Advisory Group (PAG) of community expert Aboriginal women to guide the project. Forty-three semi-structured interviews were conducted in 2013 with Aboriginal women in urban and regional prisons in NSW. We applied a grounded theory approach for the data analysis with guidance from the PAG. RESULTS: Whilst Aboriginal women reported positive and negative experiences of prison healthcare, the custodial system created numerous barriers to accessing healthcare. Aboriginal women experienced institutional racism and discrimination in the form of not being listened to, stereotyping, and inequitable healthcare compared with non-Indigenous women in prison and the community. CONCLUSIONS: 'Equal treatment' is an inappropriate strategy for providing equitable healthcare, which is required because incarcerated Aboriginal women experience significantly poorer health. Taking a decolonizing approach, we unpack and demonstrate the systems level changes needed to make health and justice agencies culturally relevant and safe. This requires further acknowledgment of the oppressive transgenerational effects of ongoing colonial policy, a true embracing of diversity of worldviews, and critically the integration of Aboriginal concepts of health at all organizational levels to uphold Aboriginal women's rights to culturally safe healthcare in prison and the community.

Supportive oncofertility care, psychological health and reproductive concerns: a qualitative study.

PURPOSE: Impaired fertility in cancer patients and survivors of reproductive age (15-45 years) may lead to psychological distress and poor mental health outcomes, and may negatively impact quality of life. Limited research has focused on the fertility experiences of those who have had access to supportive oncofertility care. This study aims to explore the fertility-care experiences and reproductive concerns of reproductive age cancer patients at the time of their cancer diagnosis who have had access to oncofertility care. METHODS: The qualitative data from a larger mixed method study is presented, comprising 30 semi-structured telephone interviews with newly diagnosed cancer patients across Australia and New Zealand, undertaken between April 2016 and April 2018. RESULTS: Interviews were undertaken with 9 male patients and 21 female patients aged between 15 and 44 years. All patients recalled a discussion about fertility and majority underwent some form of fertility preservation. Thematic analysis identified five main themes: (i) satisfaction with oncofertility care, (ii) a need for individualised treatment and support, (iii) desire for parenthood, (iv) fertility treatment can be challenging, and (v) fertility preservation provides a safety net for the future. CONCLUSIONS: Participants who access supportive oncofertility care report low emotional impact of threatened future infertility at the time of cancer diagnosis. These results suggest that such services may assist in lowering the emotional burden of potential infertility in survivors. Long-term research is needed to assess the longitudinal benefits for different models of care.

Difficult Airway Society guidelines for awake tracheal intubation (ATI) in adults.

Awake tracheal intubation has a high success rate and a favourable safety profile but is underused in cases of anticipated difficult airway management. These guidelines are a comprehensive document to support decision making, preparation and practical performance of awake tracheal intubation. We performed a systematic review of the literature seeking all of the available evidence for each element of awake tracheal intubation in order to make recommendations. In the absence of high-quality evidence, expert consensus and a Delphi study were used to formulate recommendations. We highlight key areas of awake tracheal intubation in which specific recommendations were made, which included: indications; procedural setup; checklists; oxygenation; airway topicalisation; sedation; verification of tracheal tube position; complications; management of unsuccessful awake tracheal intubation; post-tracheal intubation management; consent; and training. We recognise that there are a range of techniques and regimens that may be effective and one such example technique is included. Breaking down the key practical elements of awake tracheal intubation into sedation, topicalisation, oxygenation and performance might help practitioners to plan, perform and address complications. These guidelines aim to support clinical practice and help lower the threshold for performing awake tracheal intubation when indicated.

Project for Universal Management of Airways - part 1: concept and methods.

Multiple professional groups and societies worldwide have produced airway management guidelines. These are typically targeted at the process of tracheal intubation by a particular provider group in a restricted category of patients and reflect practice preferences in a particular geographical region. The existence of multiple distinct guidelines for some (but not other) closely related circumstances, increases complexity and may obscure the underlying principles that are common to all of them. This has the potential to increase cognitive load; promote the grouping of ideas in silos; impair teamwork; and ultimately compromise patient care. Development of a single set of airway management guidelines that can be applied across and beyond these domains may improve implementation; promote standardisation; and facilitate collaboration between airway practitioners from diverse backgrounds. A global multidisciplinary group of both airway operators and assistants was assembled. Over a 3-year period, a review of the existing airway guidelines and multiple reviews of the primary literature were combined with a structured process for determining expert consensus. Any discrepancies between these were analysed and reconciled. Where evidence in the literature was lacking, recommendations were made by expert consensus. Using the above process, a set of evidence-based airway management guidelines was developed in consultation with airway practitioners from a broad spectrum of disciplines and geographical locations. While consistent with the recommendations of the existing English language guidelines, these universal guidelines also incorporate the most recent concepts in airway management as well as statements on areas not widely addressed by the existing guidelines. The recommendations will be published in four parts that respectively address: airway evaluation; airway strategy; airway rescue and communication of airway outcomes. Together, these universal guidelines will provide a single, comprehensive approach to airway management that can be consistently applied by airway practitioners globally, independent of their clinical background or the circumstances in which airway management occurs.

Risks to healthcare workers following tracheal intubation of patients with COVID-19: a prospective international multicentre cohort study.

Healthcare workers involved in aerosol-generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID-19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID-19. Information on tracheal intubation episodes, personal protective equipment use and subsequent provider health status was collected via self-reporting. The primary endpoint was the incidence of laboratory-confirmed COVID-19 diagnosis or new symptoms requiring self-isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure-related factors and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR [range]) follow-up of 32 (18-48 [0-116]) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1% and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in women, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID-19 subsequently reported a COVID-19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID-19 transmission.

Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome.

Cardiac mitochondrial phospholipid acyl chains regulate respiratory enzymatic activity. In several diseases, the rodent cardiac phospholipidome is extensively rearranged; however, whether specific acyl chains impair respiratory enzyme function is unknown. One unique remodeling event in the myocardium of obese and diabetic rodents is an increase in docosahexaenoic acid (DHA) levels. Here, we first confirmed that cardiac DHA levels are elevated in diabetic humans relative to controls. We then used dietary supplementation of a Western diet with DHA as a tool to promote cardiac acyl chain remodeling and to study its influence on respiratory enzyme function. DHA extensively remodeled the acyl chains of cardiolipin (CL), mono-lyso CL, phosphatidylcholine, and phosphatidylethanolamine. Moreover, DHA lowered enzyme activities of respiratory complexes I, IV, V, and I+III. Mechanistically, the reduction in enzymatic activities were not driven by a dramatic reduction in the abundance of supercomplexes. Instead, replacement of tetralinoleoyl-CL with tetradocosahexaenoyl-CL in biomimetic membranes prevented formation of phospholipid domains that regulate enzyme activity. Tetradocosahexaenoyl-CL inhibited domain organization due to favorable Gibbs free energy of phospholipid mixing. Furthermore, in vitro substitution of tetralinoleoyl-CL with tetradocosahexaenoyl-CL blocked complex-IV binding. Finally, reintroduction of linoleic acid, via fusion of phospholipid vesicles to mitochondria isolated from DHA-fed mice, rescued the major losses in the mitochondrial phospholipidome and complexes I, IV, and V activities. Altogether, our results show that replacing linoleic acid with DHA lowers select cardiac enzyme activities by potentially targeting domain organization and phospholipid-protein binding, which has implications for the ongoing debate about polyunsaturated fatty acids and cardiac health.

Proteolipid domains form in biomimetic and cardiac mitochondrial vesicles and are regulated by cardiolipin concentration but not monolyso-cardiolipin.

Cardiolipin (CL) is an anionic phospholipid mainly located in the inner mitochondrial membrane, where it helps regulate bioenergetics, membrane structure, and apoptosis. Localized, phase-segregated domains of CL are hypothesized to control mitochondrial inner membrane organization. However, the existence and underlying mechanisms regulating these mitochondrial domains are unclear. Here, we first isolated detergent-resistant cardiac mitochondrial membranes that have been reported to be CL-enriched domains. Experiments with different detergents yielded only nonspecific solubilization of mitochondrial phospholipids, suggesting that CL domains are not recoverable with detergents. Next, domain formation was investigated in biomimetic giant unilamellar vesicles (GUVs) and newly synthesized giant mitochondrial vesicles (GMVs) from mouse hearts. Confocal fluorescent imaging revealed that introduction of cytochrome c into membranes promotes macroscopic proteolipid domain formation associated with membrane morphological changes in both GUVs and GMVs. Domain organization was also investigated after lowering tetralinoleoyl-CL concentration and substitution with monolyso-CL, two common modifications observed in cardiac pathologies. Loss of tetralinoleoyl-CL decreased proteolipid domain formation in GUVs, because of a favorable Gibbs-free energy of lipid mixing, whereas addition of monolyso-CL had no effect on lipid mixing. Moreover, murine GMVs generated from cardiac acyl-CoA synthetase-1 knockouts, which have remodeled CL acyl chains, did not perturb proteolipid domains. Finally, lowering the tetralinoleoyl-CL content had a stronger influence on the oxidation status of cytochrome c than did incorporation of monolyso-CL. These results indicate that proteolipid domain formation in the cardiac mitochondrial inner membrane depends on tetralinoleoyl-CL concentration, driven by underlying lipid-mixing properties, but not the presence of monolyso-CL.

Defining definitions: a Delphi study to develop a core outcome set for conditions of severe maternal morbidity.

OBJECTIVE: Develop a core outcome set of international consensus definitions for severe maternal morbidities. DESIGN: Electronic Delphi study. SETTING: International. POPULATION: Eight expert panels. METHODS: All 13 high-income countries represented in the International Network of Obstetric Surveillance Systems (INOSS) nominated five experts per condition of morbidity, who submitted possible definitions. From these suggestions, a steering committee distilled critical components: eclampsia: 23, amniotic fluid embolism: 15, pregnancy-related hysterectomy: 11, severe primary postpartum haemorrhage: 19, uterine rupture: 20, abnormally invasive placentation: 12, spontaneous haemoperitoneum in pregnancy: 16, and cardiac arrest in pregnancy: 10. These components were assessed by the expert panel using a 5-point Likert scale, following which a framework for an encompassing definition was constructed. Possible definitions were evaluated in rounds until a rate of agreement of more than 70% was reached. Expert commentaries were used in each round to improve definitions. MAIN OUTCOME MEASURES: Definitions with a rate of agreement of more than 70%. RESULTS: The invitation to participate in one or more of eight Delphi processes was accepted by 103 experts from 13 high-income countries. Consensus definitions were developed for all of the conditions. CONCLUSION: Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process. These should be used in national registrations and international studies, and should be taken up by the Core Outcomes in Women's and Newborn Health initiative. TWEETABLE ABSTRACT: Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process.

Five-year follow up of a low glycaemic index dietary randomised controlled trial in pregnancy-no long-term maternal effects of a dietary intervention.

OBJECTIVE: To determine whether a dietary intervention in pregnancy had a lasting effect on maternal outcomes of diet, HbA1c and weight retention 5 years post-intervention; and to establish whether modifiable maternal behaviours were associated with these outcomes. DESIGN: Randomised control trial of low glycaemic index (GI) diet in pregnancy with longitudinal follow up to 5 years post-intervention. SETTING: Dublin, Ireland (2007-2016). POPULATION: In all, 403 women of 759 (53.1%) were followed up at 5 years. A total of 370 (intervention n = 188; control n = 182) were included in this analysis. METHODS: Fasting glucose was measured at 13 and 28 weeks' gestation and HbA1c (mmol/mol) at 5-year follow up. Weight retention (kg) from early pregnancy to 5 years post-intervention was calculated. Dietary intakes, anthropometry, and lifestyle factors were measured in pregnancy and 5 years post-intervention. Multiple linear regression models, controlling for confounders, were used for analysis. OUTCOME: Maternal diet, HbA1c, and weight retention at 5 years post-intervention. RESULTS: There was no difference between the intervention and control at 5 years post-intervention for any long-term maternal outcomes measured. HbA1c at 5 years post-intervention was associated with early-pregnancy fasting glucose (B 1.70, 95% CI 0.36-3.04) and parity ≥3 (B 1.04, 95% CI 0.09-1.99). Weight retention was associated with change in well-being from pregnancy to 5 years (B -0.06, 95% CI -0.11 to -0.02), gestational weight gain (B 0.19, 95% CI 0.00-0.38), and GI (B 0.26, 95% CI 0.06-0.46) at 5 years. CONCLUSIONS: The ROLO low-GI dietary intervention in pregnancy had no impact on maternal dietary intakes, HbA1c or body composition 5 years post-intervention. Maternal factors and lifestyle behaviours in pregnancy have long-term effects on glucose metabolism and weight retention up to 5 years later. TWEETABLE ABSTRACT: Pregnancy factors are associated with maternal glucose metabolism and weight retention 5 years later-findings from the ROLO Study.

B Cell Activity Is Impaired in Human and Mouse Obesity and Is Responsive to an Essential Fatty Acid upon Murine Influenza Infection.

Obesity is associated with increased risk for infections and poor responses to vaccinations, which may be due to compromised B cell function. However, there is limited information about the influence of obesity on B cell function and underlying factors that modulate B cell responses. Therefore, we studied B cell cytokine secretion and/or Ab production across obesity models. In obese humans, B cell IL-6 secretion was lowered and IgM levels were elevated upon ex vivo anti-BCR/TLR9 stimulation. In murine obesity induced by a high fat diet, ex vivo IgM and IgG were elevated with unstimulated B cells. Furthermore, the high fat diet lowered bone marrow B cell frequency accompanied by diminished transcripts of early lymphoid commitment markers. Murine B cell responses were subsequently investigated upon influenza A/Puerto Rico/8/34 infection using a Western diet model in the absence or presence of docosahexaenoic acid (DHA). DHA, an essential fatty acid with immunomodulatory properties, was tested because its plasma levels are lowered in obesity. Relative to controls, mice consuming the Western diet had diminished Ab titers whereas the Western diet plus DHA improved titers. Mechanistically, DHA did not directly target B cells to elevate Ab levels. Instead, DHA increased the concentration of the downstream specialized proresolving lipid mediators (SPMs) 14-hydroxydocosahexaenoic acid, 17-hydroxydocosahexaenoic acid, and protectin DX. All three SPMs were found to be effective in elevating murine Ab levels upon influenza infection. Collectively, the results demonstrate that B cell responses are impaired across human and mouse obesity models and show that essential fatty acid status is a factor influencing humoral immunity, potentially through an SPM-mediated mechanism.

Global Capnography Project (GCAP): implementation of capnography in Malawi - an international anaesthesia quality improvement project.

The Lancet Commission on Global Surgery emphasised the importance of access to safe anaesthesia care. Capnography is an essential monitor for safe anaesthesia, but is rarely available in low-income countries. The aim of this study was twofold: to measure the prevalence of capnography in the operating theatres and in intensive care units; and to determine whether its introduction was feasible and could improve the early recognition of critical airway incidents in a low-income country. This is the first project to do this. Forty capnographs were donated to eight hospitals in Malawi. Thirty-two anaesthesia providers received a 1-day capnography training course with pre- and post-course knowledge testing. Providers kept logbooks of capnography use and recorded their responses to abnormal readings. On follow-up at 6 months, providers completed questionnaires on any significant patient safety incidents identified using capnography. In January 2017, at the commencement of the project, only one operating theatre had a capnograph. Overall, 97% and 100% 'capnography gaps' were identified in the theatres and intensive care units, respectively. The mean (SD) scores of our capnography multiple choice questionnaires improved after training from 15.00 (3.16) to 18.70 (0.99), p = < 0.001. The capnography equipment was appropriately robust and performed well. Six months following implementation, 24 (77%) anaesthesia providers reported recognising 44 oesophageal intubations and 28 (90%) believed that capnography had saved lives. This study has shown it is feasible to introduce capnography in a low-income country, resulting in early recognition of critical airway incidents and ultimately helping to save lives. Building on the experience of the first trial of pulse oximetry implementation in low-income countries in 2007, we believe this is one of the most important projects in anaesthesia safety in the last decade.