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Cardiovascular diseases (CVD) are the leading cause of death worldwide, and smoking remains the most significant preventable risk factor. The contribution of nicotine, the addictive component of all tobacco products, to smoking-related CVD remains poorly understood. In addition to smoking, obesity is also a major risk factor for the development of CVD. Recent studies indicate that individuals who are overweight or obese are at greater risk of nicotine product usage. With more than 40% of the US population affected by obesity, the combined effects of obesity and nicotine on cardiovascular (CV) health warrant urgent investigation. In the present study we investigated the combined effects of nicotine exposure and a high fat diet (HFD) on CV function.Male C57BL/6N mice (8 wk-old) were placed on either a HFD (60 kcal% Fat) or standard chow (SC, 22 kcal% Fat) and exposed to room air (RA) or nicotine vapor (NIC, 12 hr/day during the active phase) for 10 weeks (n=10-15/group). Mice with HFD exposure alone exhibited significantly greater weight gain at 10 weeks vs. SC-RA controls (122.5±9.8% increase in body weight in HFD-RA vs. 40.7±3.3% in SC-RA, p < 0.0001), whereas concurrent nicotine inhalation significantly reduced this weight gain (66.5±5.8% in HFD-NIC group, p < 0.0001). In the HFD-NIC group, blood pressure (BP) monitoring via telemetry (24 hours) revealed non-significant increases in BP in the inactive phase, coupled with a significant (p < 0.05) reduction in the expected dipping in BP during the inactive compared to the active phase (HFD-NIC: 4.5±1.2; SC-RA: 11.3±2.2; HFD-RA: 12.4±1.0 and SC-NIC: 9.7±4.6 mmHg). LV catheterization showed that mice exposed to both nicotine and HFD had elevated LV end diastolic pressure (HFD-NIC: 14.1±0.7; SC-RA: 4.5±0.8; HFD-RA: 2.8±0.7 and SC-NIC: 3.9±1.3 mmHg; p National Institute of Health [grant numbers HL135635 (to JDG, EL and XY); HL146098, HL146514, and HL151398 (to DJL.); and F30HL160071 (to AKW)]; Department of Veterans Affairs (BX004294 to EL) and the American Heart Association [Award 829761 (to AKW) and Award 20POST35200075 (to ZL)]. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Objective The prevalence of obesity is growing globally. Adiposity increases the risk for metabolic syndrome, type 2 diabetes and cardiovascular disease. Adipose tissue distribution influences systemic metabolism and impacts metabolic disease risk. The link between sexual dimorphisms of adiposity and metabolism is poorly defined. We hypothesise that depot-specific adipose tissue mitochondrial function contributes to the sexual dimorphism of metabolic flexibility in obesity. Methods Male and female mice fed high fat diet (HFD) or standard diet (STD) from 8–18 weeks of age underwent whole animal calorimetry and high-resolution mitochondrial respirometry analysis on adipose tissue depots. To determine translatability we used RT-qPCR to examine key brown adipocyte-associated gene expression: peroxisome proliferator-activated receptor co-activator 1α, Uncoupling protein 1 and cell death inducing DFFA like effector a in brown adipose tissue (BAT) and subcutaneous adipose tissue (sWAT) of 18-week-old mice and sWAT from human volunteers. Results Male mice exhibited greater weight gain compared to female mice when challenged with HFD. Relative to increased body mass, the adipose to body weight ratio for BAT and sWAT depots was increased in HFD-fed males compared to female HFD-fed mice. Oxygen consumption, energy expenditure, respiratory exchange ratio and food consumption did not differ between males and females fed HFD. BAT mitochondria from obese females showed increased Complex I & II respiration and maximal respiration compared to lean females whereas obese males did not exhibit adaptive mitochondrial BAT respiration. Sexual dimorphism in BAT-associated gene expression in sWAT was also associated with Body Mass Index in humans. Conclusions We show that sexual dimorphism of weight gain is reflected in mitochondrial respiration analysis. Female mice have increased metabolic flexibility to adapt to changes in energy intake by regulating energy expenditure through increased complex II and maximal mitochondrial respiration within BAT when HFD challenged and increased proton leak in sWAT mitochondria.

Use of electronic cigarettes is rapidly increasing among youth and young adults, but little is known regarding the long-term cardiopulmonary health impacts of these nicotine-containing devices. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension (PH) and right ventricular (RV) remodeling in mice. These changes were associated with upregulated RV angiotensin-converting enzyme (ACE). Angiotensin II receptor blockers (ARBs) have been shown to reverse cigarette smoking-induced PH in rats. ACE inhibitor and ARB use in a large retrospective cohort of patients with PH is associated with improved survival. Here, we utilized losartan (an ARB specific for angiotensin II type 1 receptor) to further explore nicotine-induced PH. Male C57BL/6 mice received nicotine vapor for 12 h/day, and exposure was assessed using serum cotinine to achieve levels comparable to human smokers or electronic cigarette users. Mice were exposed to nicotine for 8 wk and a subset was treated with losartan via an osmotic minipump. Cardiac function was assessed using echocardiography and catheterization. Although nicotine exposure increased angiotensin II in the RV and lung, this finding was nonsignificant. Chronic, inhaled nicotine significantly increased RV systolic pressure and RV free wall thickness versus air control. These parameters were significantly lower in mice receiving both nicotine and losartan. Nicotine significantly increased RV internal diameter, with no differences seen between the nicotine and nicotine-losartan group. Neither nicotine nor losartan affected left ventricular structure or function. These findings provide the first evidence that antagonism of the angiotensin II type 1 receptor can ameliorate chronic, inhaled nicotine-induced PH and RV remodeling. NEW & NOTEWORTHY Chronic, inhaled nicotine causes pulmonary hypertension and right ventricular remodeling in mice. Treatment with losartan, an angiotensin II type 1 receptor antagonist, ameliorates nicotine-induced pulmonary hypertension and right ventricular remodeling. This novel finding provides preclinical evidence for the use of renin-angiotensin system-based therapies in the treatment of pulmonary hypertension, particularly in patients with a history of tobacco-product use.

Background Patients with coexistent chronic heart failure (CHF) and diabetes mellitus (DM) demonstrate greater exercise limitation and worse prognosis compared with CHF patients without DM, even when corrected for cardiac dysfunction. Understanding the origins of symptoms in this subgroup may facilitate development of targeted treatments. We therefore characterized the skeletal muscle phenotype and its relationship to exercise limitation in patients with diabetic heart failure (D‐HF). Methods In one of the largest muscle sampling studies in a CHF population, pectoralis major biopsies were taken from age‐matched controls (n = 25), DM (n = 10), CHF (n = 52), and D‐HF (n = 28) patients. In situ mitochondrial function and reactive oxygen species, fibre morphology, capillarity, and gene expression analyses were performed and correlated to whole‐body exercise capacity. Results Mitochondrial respiration, content, coupling efficiency, and intrinsic function were lower in D‐HF patients compared with other groups (P < 0.05). A unique mitochondrial complex I dysfunction was present in D‐HF patients only (P < 0.05), which strongly correlated to exercise capacity (R 2 = 0.64; P < 0.001). Mitochondrial impairments in D‐HF corresponded to higher levels of mitochondrial reactive oxygen species (P < 0.05) and lower gene expression of anti‐oxidative enzyme superoxide dismutase 2 (P < 0.05) and complex I subunit NDUFS1 (P < 0.05). D‐HF was also associated with severe fibre atrophy (P < 0.05) and reduced local fibre capillarity (P < 0.05). Conclusions Patients with D‐HF develop a specific skeletal muscle pathology, characterized by mitochondrial impairments, fibre atrophy, and derangements in the capillary network that are linked to exercise intolerance. These novel preliminary data support skeletal muscle as a potential therapeutic target for treating patients with D‐HF.

The endoplasmic reticulum (ER) regulates cellular protein and lipid biosynthesis. ER dysfunction leads to protein misfolding and the unfolded protein response (UPR), which limits protein synthesis to prevent cytotoxicity. Chronic ER stress in skeletal muscle is a unifying mechanism linking lipotoxicity to metabolic disease. Unidentified signals from cells undergoing ER stress propagate paracrine and systemic UPR activation. Here, we induce ER stress and lipotoxicity in myotubes. We observe ER stress-inducing lipid cell non-autonomous signal(s). Lipidomics identifies that palmitate-induced cell stress induces long-chain ceramide 40:1 and 42:1 secretion. Ceramide synthesis through the ceramide synthase 2 de novo pathway is regulated by UPR kinase Perk. Inactivation of CerS2 in mice reduces systemic and muscle ceramide signals and muscle UPR activation. The ceramides are packaged into extracellular vesicles, secreted and induce UPR activation in naïve myotubes through dihydroceramide accumulation. This study furthers our understanding of ER stress by identifying UPR-inducing cell non-autonomous signals.

Brown and beige adipose tissue are emerging as distinct endocrine organs. These tissues are functionally associated with skeletal muscle, adipose tissue metabolism and systemic energy expenditure, suggesting an interorgan signaling network. Using metabolomics, we identify 3-methyl-2-oxovaleric acid, 5-oxoproline, and β-hydroxyisobutyric acid as small molecule metabokines synthesized in browning adipocytes and secreted via monocarboxylate transporters. 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid induce a brown adipocyte-specific phenotype in white adipocytes and mitochondrial oxidative energy metabolism in skeletal myocytes both in vitro and in vivo. 3-methyl-2-oxovaleric acid and 5-oxoproline signal through cAMP-PKA-p38 MAPK and β-hydroxyisobutyric acid via mTOR. In humans, plasma and adipose tissue 3-methyl-2-oxovaleric acid, 5-oxoproline and β-hydroxyisobutyric acid concentrations correlate with markers of adipose browning and inversely associate with body mass index. These metabolites reduce adiposity, increase energy expenditure and improve glucose and insulin homeostasis in mouse models of obesity and diabetes. Our findings identify beige adipose-brown adipose-muscle physiological metabokine crosstalk., Beige and brown fat may influence systemic metabolism through secreted signals. Here the authors identify a panel of metabolites secreted from beige and brown fat cells, which signal to influence fat tissue and skeletal muscle metabolism and have anti-obesity effects in mouse models of obesity and diabetes.

Cigarette smoking is the single most important risk factor for the development of cardiovascular diseases (CVDs). However, the role of nicotine, the addictive component of all tobacco products, in the development of CVD is incompletely understood. Although increased public awareness of the harms of cigarette smoking has successfully led to a decline in its prevalence, the use of electronic cigarettes (e-cig) or electronic nicotine delivery system has increased dramatically in recent years because of the perception that these products are safe. This review summarizes our current knowledge of the expression and function of the nicotinic acetylcholine receptors in the cardiovascular system and the impact of nicotine exposure on cardiovascular health, with a focus on nicotine-induced vascular dysfunction. Nicotine alters vasoreactivity through endothelium-dependent and/or endothelium-independent mechanisms, leading to clinical manifestations in both cigarette smokers and e-cig users. In addition, nicotine induces vascular remodelling through its effects on proliferation, migration and matrix production of both vascular endothelial and vascular smooth muscle cells. The purpose of this review is to identify critical knowledge gaps regarding the effects of nicotine on the vasculature and to stimulate continued nicotine research.

Brown and beige adipose tissue are emerging as distinct endocrine organs. These tissues are functionally associated with skeletal muscle, adipose tissue metabolism and systemic energy expenditure, suggesting an inter-organ signaling network. Using a metabolomic approach we identified 3-methyl-2-oxovaleric acid (MOVA), 5-oxoproline (5OP), and β-hydroxyisobutyric acid (BHIBA) as small molecule metabokines synthesized in browning adipocytes and secreted via monocarboxylate transporters. MOVA, 5OP and BHIBA induce a brown adipocyte-specific phenotype in white adipocytes and mitochondrial oxidative energy metabolism in skeletal myocytes both in vitro and in vivo. MOVA and 5OP signal through cAMP-PKA-p38 MAPK and BHIBA via mTOR. These metabolites reduce adiposity, increase energy expenditure and improve glucose and insulin homeostasis in mouse models of obesity and diabetes. In humans, plasma and adipose tissue MOVA, 5OP and BHIBA concentrations are correlated with markers of adipose browning and inversely associated with BMI. Our findings identify beige adipose-brown adipose-muscle physiological metabokine crosstalk.

Genetic analyses provide a powerful tool with which to identify the biological components of historical objects. Te Tiriti o Waitangi | The Treaty of Waitangi is New Zealand's founding document, intended to be a partnership between the indigenous Māori and the British Crown. Here we focus on an archived piece of blank parchment that has been proposed to be the missing portion of the lower parchment of the Waitangi Sheet of the Treaty. However, its physical dimensions and characteristics are not consistent with this hypothesis. We perform genetic analyses on the parchment membranes of the Treaty, plus the blank piece of parchment. We find that all three parchments were made from ewes and that the blank parchment is highly likely to be a portion cut from the lower membrane of the Waitangi Sheet because they share identical whole mitochondrial genomes, including an unusual heteroplasmic site. We suggest that the differences in size and characteristics between the two pieces of parchment may have resulted from the Treaty's exposure to water in the early 20th century and the subsequent repair work, light exposure during exhibition or the later conservation treatments in the 1970s and 80s. The blank piece of parchment will be valuable for comparison tests to study the effects of earlier treatments and to monitor the effects of long-term display on the Treaty.

ABSTRACT INTRODUCTION Subsidisation of the levonorgestrel-releasing Jadelle® contraceptive implant in 2010 resulted in a rapid uptake. Clinicians had little prior experience of client satisfaction, side effect profile, and removal rate of this contraceptive method. AIM To obtain information on satisfaction, bleeding patterns, continuation rates and reasons for removal for New Zealand women during their first year of use of a subsidised contraceptive implant, Jadelle®. METHODS Women having a Jadelle® implant inserted in New Zealand Family Planning clinics were recruited to be followed up by phone, text or email at 1, 3, 6, 9 and 12 months. They were asked about their bleeding pattern, satisfaction and their views on benefits of, or problems with, implant use. RESULTS 252 women were recruited. The three common bleeding patterns in the cohort were regular periods, amenorrhoea and irregular bleeding. Eighteen percent had their implant removed within the first year with more than half of those being unhappy with their bleeding pattern. This was usually prolonged bleeding. Otherwise satisfaction rates were high throughout the year. DISCUSSION The majority of New Zealand women using Jadelle® were satisfied with this method of contraception during their first year of use. Implant removals were most likely to be related to prolonged bleeding. However the commonest bleeding pattern was regular periods. KEYWORDS Contraceptive implant; progestin; bleeding; satisfaction; continuation rate; reducing reproductive health inequalities

Aim To investigate the acceptability and satisfaction with the Aboriginal Community Antenatal Program by staff in the program and partner agencies. Design A Strengths, Weaknesses, Opportunities and Threats framework guided the research and data collection methods. Mixed methodology was used, accessing qualitative and quantitative information from data bases, program and supporting agency staff. Quantitative data were analysed through a social sciences statistical package. Qualitative data were identified through questionnaires and analysed using thematic analysis. Setting Remote Aboriginal communities in the Goldfields region of Western Australia. Participant sources Twenty two participants including program and supporting agency staff. Main outcome measures This study measures acceptability and satisfaction of program antenatal and pre-conception activities by program staff and partner agencies. Results Qualitative results indicate acceptability and satisfaction with the program, identifying a range of organisational, staffing, cultural and interagency issues relating to a model of service provision. Quantitative data suggested positive program outputs from service delivery. Conclusion Findings suggest the Aboriginal Community Antenatal Program and partner agencies are increasing provision of community based pre-conception and antenatal health services and enhancing collaboration between a range of health provider agencies, with partnerships between Aboriginal and non-Aboriginal program staff contributing to an emerging model of community antenatal care.

AIM: This study aims to describe pregnancy outcomes for a population-based sample of New Zealand women, and to explore the relationship between lifetime experience of intimate partner violence (IPV) and two non-birth pregnancy outcomes: spontaneous abortion (miscarriage) and termination of pregnancy (abortion). METHODS: Face-to-face interviews were conducted with a random sample of 2391 women who had ever been pregnant, aged 18-64 years old, in two regions (urban and rural). Both outcome measures were determined by asking women if they had ever had a miscarriage or an abortion. Analyses were conducted using logistic regression. RESULTS: Almost one in three ever-pregnant women reported having at least one miscarriage, and at least one in ten reported terminating a pregnancy. Even controlling for potential confounders, women who had ever experienced IPV were 1.4 times more likely to report they had ever had a miscarriage compared with women who had never experienced violence (P = 0.008), and were 2.5 times more likely to report they had ever had an abortion (P < 0.0001). Ethnicity was significantly associated with experiencing a miscarriage (Asian and Pacific women were less likely compared with European/Pakeha women), and having ever had an abortion (Asian women were 3.5 times more likely compared with Pakeha women). CONCLUSIONS: In this population-based sample, miscarriage was relatively common, as was termination of pregnancy. IPV was significantly associated with both induced and spontaneous abortion. Healthcare settings that see women experiencing these pregnancy outcomes need to be cognisant of the link with current and historical IPV, and be able to respond to women appropriately. Language: en

To explore the reasons why women have an abortion soon after delivering an infant and what could reduce unintended pregnancy and abortion in this group of women.Data were collected from anonymous self-complete questionnaires from women who presented to a first trimester Termination of Pregnancy service and who had delivered a live-born infant within the preceding 6 months; and also from the healthcare professionals who are responsible for maternity care to identify the reasons behind the unintended pregnancies, and around Lead Maternity Caregivers' (LMCs') usual practice of postnatal contraceptive provisions, and any barriers to its provision.22 women were recruited into the study and completed the questionnaire. The majority of women (19) reported that they had discussed contraception with the LMC. However only 4 women were given a prescription for the pill and 2 women were given a prescription for condoms (which was not filled). Almost all women had previously accessed contraception from another provider. 59 LMCs responded. All LMCs reported that they discuss contraception with women, However the majority reported that they discuss contraception with all women at discharge (50) and/or postnatally (49). Only 23 LMCs reported discussing contraception antenatally or at booking.Opportunities to intervene are being missed. These include: discussing contraception with all women at booking and/or antenatally; for LMCs to offer prescriptions for contraception to all women and to encourage them to access the supplies, for LMCs to be trained so they feel confident to advise and supply all contraceptive options. Improvements for women could also be made by providing postnatal women with free consultations to her choice of provider, during pregnancy to organise postnatal contraception.

To explore the extent of intimate partner violence during pregnancy and its association with pregnancy intendedness and pregnancy-related behaviours among a representative sample of New Zealand women.Face-to-face interviews were conducted with a representative sample of 2391 women who had ever been pregnant, aged 18-64 years old in two regions (urban and rural) in New Zealand.Six per cent of urban women and 9% of rural women had ever experienced violence during pregnancy; approximately 40% of these had experienced violence in more than one pregnancy. Women who had experienced violence in pregnancy, compared with those who had not, were less likely to report their last pregnancy had been wanted at that time (28% vs 55%), and less likely to report that their partner wanted the pregnancy (40% vs 57%). Antenatal and postnatal care attendance was almost universal during the last pregnancy. Women who had experienced violence during pregnancy were more likely to smoke tobacco during pregnancy (67% vs 22%, P0.0001), and more commonly, consumed alcohol (31% vs 20%, not significant). For the most recent pregnancy in which women had experienced violence, most was perpetrated by the child's biological father (96%), and most women (74%) reported that the same man had also beaten her before she was pregnant.Violence during pregnancy is a significant problem for New Zealand women, with negative health implications for both women and their children. Active intervention and support is necessary to mitigate potential consequences.

Aim: To outline the use of contraception among a representative sample of New Zealand women, and explore associations with intimate partner violence (IPV), and contraception and condom use. Methods: Face-to-face interviews were conducted with a random sample of 2790 women who had ever had sexual intercourse, aged 18–64 years old in two regions (urban and rural) in New Zealand. Analyses were conducted using logistic regression and Wald χ2 tests. Results: Almost all women had used contraception at some point in their life, and almost one half of all women 18–49 years were currently using methods of contraception. Contraceptive use and methods varied significantly by location. Women who had ever experienced IPV were significantly more likely to report having ever used contraception, compared with women who had not experienced IPV (91% vs 85.2%). While having a partner who refused to use or tried to stop women from using a method of contraception was rare, it was significantly more common among women who had ever experienced IPV (5.4% vs 1.3%). Conclusions: Most women have used contraception at some point. Women who have ever experienced IPV were: more likely to have used contraception than women who have not experienced IPV, and to have had partners who refused to use condoms or prevented women from using contraception. Partner refusal may be a key indicator of IPV. These findings emphasise the importance of family violence screening at routine health consultations.

Aims: To measure the prevalence of family violence reported by women seeking a termination of pregnancy (TOP). Methods: A cross sectional survey involving consecutive women at one Health Waikato abortion clinic. Participants completed a self-administered questionnaire in private counselling rooms. Results: Sixty-two of the 125 women invited to participate did so (response rate: 49.6%). The reported lifetime prevalence of physical or sexual abuse was 50.8%. The reported lifetime prevalence of physical abuse was 43.3% and that of sexual abuse was 32.2%. The reported prevalence of physical abuse within the last year was 13.3%, and of sexual abuse within the last year was 8.5%. Of women reporting a lifetime history of physical abuse, 69% reported that her partner was the perpetrator/one of the perpetrators of abuse. Conclusions: The study demonstrated a high prevalence of family violence amongst women attending an abortion clinic. Consideration should be given to screening for family violence in abortion clinics in New Zealand. Screening should be accompanied by the provision of appropriate information and support for women with family violence issues.