The effects of air pollution on health outcomes are well-established. However, little is known about perceptions of air pollution and how it may influence exercise behaviours. The aim of this study was to understand the perceived importance of air pollution during planned exercise, and where relevant, explore how those perceptions may differ between those living in different locations. A questionnaire was disseminated to several running and cycling clubs in the United Kingdom, covering population characteristics to determine urban, rural or coastal residents and exercisers, self-reported asthma, perceptions of air quality during active travel, planned exercise and attitudes towards learning more about the topic. Anonymised responses were gained from 381 adult participants (≥18 years and 60% female), 119 of whom answered questions related to active travel. More than half (54%) of all respondents think about the air quality they are exposed to during exercise and how it may affect their health. More urban than rural respondents (59% vs. 47% and p = 0.03) think about air quality and the impact it may have on their health when exercising. There were insufficient coastal respondents for direct comparison. Most survey respondents (57%) state that they would take the most severe course of action regarding exercise behaviour by avoiding it altogether during periods of heavy road traffic. Individuals with self-reported asthma (n = 60), irrespective of place of residence, are the most likely to be conscious of the potential effects of air pollution on their health and exercise performance compared to counterparts without self-reported asthma.

In humans born at term, maximal nephron number is reached by the time nephrogenesis is completed - at approximately 36 weeks' gestation. The number of nephrons does not increase further and subsequently remains stable until loss occurs through ageing or disease. Nephron endowment is key to the functional capacity of the kidney and its resilience to disease; hence, any processes that impair kidney development in the developing fetus can have lifelong adverse consequences for renal health and, consequently, for quality and length of life. The timing of nephrogenesis underlies the vulnerability of developing human kidneys to adverse early life exposures. Indeed, exposure of the developing fetus to a suboptimal intrauterine environment during gestation - resulting in intrauterine growth restriction (IUGR) - and/or preterm birth can impede kidney development and lead to reduced nephron endowment. Furthermore, emerging research suggests that IUGR and/or preterm birth is associated with an elevated risk of chronic kidney disease in later life. The available data highlight the important role of early life development in the aetiology of kidney disease and emphasize the need to develop strategies to optimize nephron endowment in IUGR and preterm infants.

Background/Aims In the Norfolk and Waveney Integrated Care System, a community organisation and a hospice have collaborated to develop an innovative specialist palliative care service in a community hospital. The aim of this service evaluation was to review the specialist palliative care service 2 years after implementation began across the integrated care system. Methods A multi-method approach was used to evaluate this service. Data were collected from pre-existing datasets on referrals, discharge and service use and described using descriptive statistics to assess how the service was used during the evaluation period (1 April 2019–31 March 2021). Qualitative data were collected via semi-structured interviews with 25 patients, carers, staff and other stakeholders. Interview transcripts were analysed using thematic analysis. Results During the 2-year evaluation period, the service recorded 1800 referrals, 189 admissions to specialist beds and 19 712 telephone calls to the 24-hour advice line. Thematic analysis of interview transcripts identified four themes: impact of the specialist palliative care beds, implementation of changes to practice, communication and coordination, and challenges related to providing the service. Overall, patients and carers had very positive views of the quality of care they received. Staff also identified benefits, including access to training and improved morale. Challenges included the limited number of beds and difficulties balancing the care needs of palliative care patients with other patients in the inpatient ward. Conclusions The specialist palliative care service promoted collaborative working, leading to enhanced knowledge and skills for staff supporting patients with specialist palliative care needs. The service was well-used and patients and their carers were generally very satisfied with the care they received.

BACKGROUND Postnatal corticosteroids are used in the critical care of preterm infants for the prevention and treatment of bronchopulmonary dysplasia. We aimed to investigate the effects of early postnatal dexamethasone therapy and dose on cardiac maturation and morphology in preterm lambs. METHODS Lambs were delivered prematurely at ~128 days of gestational age and managed postnatally according to best clinical practice. Preterm lambs were administered dexamethasone daily at either a low-dose (n = 9) or a high-dose (n = 7), or were naïve to steroid treatment and administered saline (n = 9), over a 7-day time-course. Hearts were studied at postnatal Day 7 for gene expression and assessment of myocardial structure. RESULTS High-dose dexamethasone treatment in the early postnatal period led to marked differences in cardiac gene expression, altered cardiomyocyte maturation and reduced cardiomyocyte endowment in the right ventricle, as well as increased inflammatory infiltrates into the left ventricle. Low-dose exposure had minimal effects on the preterm heart. CONCLUSION Neonatal dexamethasone treatment led to adverse effects in the preterm heart in a dose-dependent manner within the first week of life. The observed cardiac changes associated with high-dose postnatal dexamethasone treatment may influence postnatal growth and remodeling of the preterm heart and subsequent long-term cardiac function.

Background Antenatal conditions that are linked with preterm birth, such as intrauterine inflammation, can influence fetal cardiac development thereby rendering the heart more vulnerable to the effects of prematurity. We aimed to investigate the effect of intrauterine inflammation, consequent to lipopolysaccharide exposure, on postnatal cardiac growth and maturation in preterm lambs. Methods Preterm lambs (~129 days gestational age) exposed antenatally to lipopolysaccharide or saline were managed according to contemporary neonatal care and studied at postnatal day 7. Age-matched fetal controls were studied at ~136 days gestational age. Cardiac tissue was sampled for molecular analyses and assessment of cardiac structure and cardiomyocyte maturation. Results Lambs delivered preterm showed distinct ventricular differences in cardiomyocyte growth and maturation trajectories as well as remodeling of the left ventricular myocardium compared to fetal controls. Antenatal exposure to lipopolysaccharide resulted in further collagen deposition in the left ventricle and a greater presence of immune cells in the preterm heart. Conclusions Adverse impacts of preterm birth on cardiac structure and cardiomyocyte growth kinetics within the first week of postnatal life are exacerbated by intrauterine inflammation. The maladaptive remodeling of the cardiac structure and perturbed cardiomyocyte growth likely contribute to the increased vulnerability to cardiac dysfunction following preterm birth. Impact Preterm birth induces maladaptive cardiac remodeling and adversely impacts cardiomyocyte growth kinetics within the first week of life in sheep. These effects of prematurity on the heart are exacerbated when preterm birth is preceded by exposure to intrauterine inflammation, a common antecedent of preterm birth. Inflammatory injury to the fetal heart coupled with preterm birth consequently alters neonatal cardiac growth and maturation and thus, may potentially influence long-term cardiac function and health.

This study investigated the effect of high-intensity interval training (HIIT) cycling elevation training mask (ETM) in moderately trained participants on both aerobic (V̇O2max) and anaerobic power performance. Sixteen participants, five females (25.8 ± 7.6 years) and eleven males (22.2 ± 3.5 years) took part in this randomized controlled trial. Participants were assigned to the experimental group (ETM, n = 8 participants) wearing an ETM or the control group (CON, n = 8 participants) without the ETM. V̇O2max was determined during a standardized protocol using Cortex Metalyzer-3B on a cycle ergometer. Peak and average power were calculated a 30-second Wingate test. Participants completed 4-weeks (two sessions a week) of high-intensity cycle training. Each training session consisting of 4 separate bouts of 4-minutes of high-intensity cycling exercise. After the training period, ETM reported an increment in V̇O2max (effect size (d) = 1.19), peak power (d = 0.77), and average power (d = 0.76). CON reported an increment only in V̇O2max (d = 1.00). No-between group differences were found in any parameter (ANCOVA), therefore the two protocols should be considered equally effective. In conclusion, this study reported that both HIIT protocols significantly enhance V̇O2max in a very short training period (4 weeks).

Low birth weight is a risk factor for chronic kidney disease, whereas adult podocyte depletion is a key event in the pathogenesis of glomerulosclerosis. However, whether low birth weight due to poor maternal nutrition is associated with low podocyte endowment and glomerulosclerosis in later life is not known. Female Sprague-Dawley rats were fed a normal-protein diet (NPD; 20%) or low-protein diet (LPD; 8%), to induce low birth weight, from 3 wk before mating until postnatal day 21 (PN21), when kidneys from some male offspring were taken for quantitation of podocyte number and density in whole glomeruli using immunolabeling, tissue clearing, and confocal microscopy. The remaining offspring were fed a normal- or high-fat diet until 6 mo to induce catch-up growth and excessive weight gain, respectively. At PN21, podocyte number per glomerulus was 15% lower in low birth weight (LPD) than normal birth weight (NPD) offspring, with this deficit greater in outer glomeruli. Surprisingly, podocyte number in LPD offspring increased in outer glomeruli between PN21 and 6 mo, although an overall 9% podocyte deficit persisted. Postnatal fat feeding to LPD offspring did not alter podometric indexes or result in glomerular pathology at 6 mo, whereas fat feeding in NPD offspring was associated with far greater body and fat mass as well as podocyte loss, reduced podocyte density, albuminuria, and glomerulosclerosis. This is the first report that maternal diet can influence podocyte endowment. Our findings provide new insights into the impact of low birth weight, podocyte endowment, and postnatal weight on podometrics and kidney health in adulthood.NEW & NOTEWORTHY The present study shows, for the first time, that low birth weight as a result of maternal nutrition is associated with low podocyte endowment. However, a mild podocyte deficit at birth did not result in glomerular pathology in adulthood. In contrast, postnatal podocyte loss in combination with excessive body weight led to albuminuria and glomerulosclerosis. Taken together, these findings provide new insights into the associations between birth weight, podocyte indexes, postnatal weight, and glomerular pathology.

BACKGROUND:Adults born preterm (< 37 weeks' gestation) exhibit altered cardiac growth and are susceptible to cardiac dysfunction. Sheep studies have shown that moderate preterm birth results in maladaptive structural remodelling of the cardiac ventricles. The aim of this study was to examine ventricular structure in lambs born at a greater severity of preterm birth and ventilated postnatally.METHODS:Former-preterm lambs delivered at 128 days' gestation, and mechanically ventilated for a week after birth, were compared with unventilated lambs born at term (150 days' gestation), at 2 months (term: n = 10, former-preterm: n = 8), and 5 months (term: n = 9, former-preterm: n = 8) term-equivalent age. The right ventricle and left ventricle plus septum were analysed using immunohistochemistry, histology, and stereology.RESULTS:Cardiomyocyte number, cross-sectional area, proliferation, and apoptosis were not affected by preterm birth or age. Left ventricle plus septum interstitial collagen levels increased with age (P = 0.0015) and were exacerbated by preterm birth (P = 0.0006; 2 months term: 0.57% ± 0.07%, former-preterm: 1.44% ± 0.18%; 5 months term: 1.37% ± 0.25%, former-preterm: 2.15% ± 0.31%). Right ventricle interstitial collagen levels increased with age (P = 0.012) but were not affected by preterm birth.CONCLUSION:This study is the first to explore the effect of preterm birth combined with modern neonatal interventions on the ventricular myocardium in lambs. There was no adverse impact on cardiomyocyte growth in early postnatal life. Of concern, however, there was increased collagen deposition in the preterm hearts, which has the potential to induce cardiac dysfunction, especially if it becomes exaggerated with ageing.

Preterm birth coincides with a key developmental window of cardiac growth and maturation, and thus has the potential to influence long-term cardiac function. Individuals born preterm have structural cardiac remodelling and altered cardiac growth and function by early adulthood. The evidence linking preterm birth and cardiovascular disease in later life is mounting. Advances in the perinatal care of preterm infants, such as glucocorticoid therapy, have improved survival rates, but at what cost? This review highlights the short-term and long-term impact of preterm birth on the structure and function of the heart and focuses on the impact of antenatal and postnatal glucocorticoid treatment on the immature preterm heart.

The present study sought to investigate physiological adaptations associated with an 8-week supervised climbing intervention in recreational climbers. Nine participants (5 males and 4 females; age: 37 ± 8 years; stature: 169.7 ± 10.6 cm; body mass 83.3 ± 20.3 kg) volunteered to complete the intervention concomitant with their recreational climbing activities. Blood pressure, body composition, peak aerobic capacity, total cholesterol, and handgrip strength were assessed before and after the intervention. Post-intervention, diastolic blood pressure was significantly reduced (pre: 87 ± 6 mmHg, post: 72 ± 10 mmHg, p<0.01), without significant changes in systolic blood pressure (pre: 136 ± 15 mmHg, post: 128 ± 20 mmHg, p=0.19). This resulted in a significant reduction in mean arterial pressure (pre: 103 ± 9 mmHg, post: 90 ± 13 mmHg, p<0.01). A significant reduction in total cholesterol was also observed following the 8-week climbing intervention (pre: 5.09 ± 0.49 mmol/L, post: 4.39 ± 0.63 mmol/L, p<0.01). However, there were no significant changes in body fat percentage (p=0.67), skeletal muscle mass (p=0.76), isometric hand-grip strength (dominant hand: p=0.93, non-dominant hand: p=0.12) or peak aerobic capacity (p=0.37). Supervised indoor climbing exercise may therefore serve as an important non-pharmacological intervention to improve cardiovascular health by reducing mean arterial pressure and total cholesterol levels in recreational climbers, independent of changes in body composition or peak aerobic capacity.

Diffusion tensor imaging (DTI) is an MRI technique that can be used to map cardiomyocyte tracts and estimate local cardiomyocyte and sheetlet orientation within the heart. DTI measures diffusion distances of water molecules within the myocardium, where water diffusion generally occurs more freely along the long axis of cardiomyocytes and within the extracellular matrix, but is restricted by cell membranes such that transverse diffusion is limited. DTI can be undertaken in fixed hearts and it allows the three-dimensional mapping of the cardiac microarchitecture, including cardiomyocyte organization, within the whole heart. The objective of this study was to use DTI to compare the cardiac microarchitecture and cardiomyocyte organization in archived fixed left ventricles of lambs that were born either preterm (n = 5) or at term (n = 7), at a postnatal timepoint equivalent to about 6 years of age in children. Although the findings support the feasibility of retrospective DTI scanning of fixed hearts, several hearts were excluded from DTI analysis because of poor scan quality, such as ghosting artifacts. The preliminary findings from viable DTI scans (n = 3/group) suggest that the extracellular compartment is altered and that there is an immature microstructural phenotype early in postnatal life in the LV of lambs born preterm. Our findings support a potential time-efficient imaging role for DTI in detecting abnormal changes in the microstructure of fixed hearts of former-preterm neonates, although further investigation into factors that affect scan quality is required.

Preterm birth (delivery <37 weeks of gestation) is associated with impaired glomerular capillary growth in neonates; if this persists, it may be a contributing factor in the increased risk of hypertension and chronic kidney disease in people born preterm. Therefore, in this study, we aimed to determine the long-term impact of preterm birth on renal morphology, in adult sheep. Singleton male sheep were delivered moderately preterm at 132 days (~0.9) of gestation (n = 6) or at term (147 days gestation; n = 6) and euthanised at 14.5 months of age (early adulthood). Stereological methods were used to determine mean renal corpuscle and glomerular volumes, and glomerular capillary length and surface area, in the outer, mid and inner regions of the renal cortex. Glomerulosclerosis and interstitial collagen levels were assessed histologically. By 14.5 months of age, there was no difference between the term and preterm sheep in body or kidney weight. Renal corpuscle volume was significantly larger in the preterm sheep than the term sheep, with the preterm sheep exhibiting enlarged Bowman's spaces; however, there was no difference in glomerular volume between groups, with no impact of preterm birth on capillary length or surface area per glomerulus. There was also no difference in interstitial collagen levels or glomerulosclerosis index between groups. Findings suggest that moderate preterm birth does not adversely affect glomerular structure in early adulthood. The enlarged Bowman's space in the renal corpuscles of the preterm sheep kidneys, however, is of concern and merits further research into its cause and functional consequences.

ABSTRACT Introduction Postmenopausal women have lower resting cardiac function than premenopausal women, but whether the menopause influences maximal cardiac output and hence exercise capacity is unclear. It is possible that premenopausal and postmenopausal women achieve similar improvements in maximal aerobic capacity (V˙O 2max ) and cardiac output with exercise training via different regional left ventricular muscle function (“LV mechanics”), as suggested by in vitro and animal studies. The aim of this study was to investigate the effects of the menopause on LV mechanics and adaptations to exercise training. Methods Twenty-five healthy untrained middle-age women (age, 45–58 yr; 11 premenopausal, 14 postmenopausal) completed 12 wk of exercise training. Before and after exercise training, (i) V˙O 2max and blood volume were determined, and (ii) LV mechanics were assessed using echocardiography at rest and during two submaximal physiological tests — lower-body negative pressure and supine cycling. Results The increase in V˙O 2max after exercise training was 9% smaller in postmenopausal than premenopausal women, concomitant with a smaller increase in blood volume ( P < 0.05). However, cardiac output and LV volumes were not different between premenopausal and postmenopausal women ( P > 0.05) despite altered regional LV muscle function, as indicated by higher basal mechanics in premenopausal women during the physiological tests after exercise training ( P < 0.05). Conclusions These findings are the first to confirm altered LV mechanics in postmenopausal women. In addition, the reduced aerobic adaptability to exercise training in postmenopausal women does not appear to be a central cardiac limitation and may be due to altered blood volume distribution and lower peripheral adaptations.

This Special Issue is devoted to studies relating to the kidneys and is published in honor of Professor John Bertram (Figure 1), who has spent most of his research career studying kidneys. As the Associate Editor of The Anatomical Record of the Australasian region, my idea of devoting a Special Issue relating to kidney development and disease was originally sparked by the recent Special Issue in The Anatomical Record on heart development in honor of Roger Markwald (https://anatomypubs.onlinelibrary.wiley.com/toc/19328494/2019/302/1). So, this got me to thinking, would not it be good to now have a Special Issue specifically focusing on the kidneys, in honor of John Bertram who had recently stepped down as the Chair of the Department of Anatomy and Developmental Biology at Monash University (one of Australia's top universities). John has been a member of the AAA for over 30 years, was Chair of the Department of Anatomy and Developmental Biology at Monash University for 18 years, has published on multiple occasions in The Anatomical Record and has spent most of his research career in kidney research. His expertise in stereology is sought by researchers worldwide and his landmark studies in relation to nephron number in human kidneys have led to rewriting the medical textbooks! I have known and worked with John for a very long time. I have been collaborating with him for about 25 years; initially, our collaboration was developed based on his stereology expertise, where as a cardiovascular cell biologist I was looking at the effect of angiotensin II on the growth of smooth muscle cells within the blood vessel wall. From there, it was the influence of John's research that sparked my interest in the kidneys, and in particular, how nephron endowment at birth influences blood pressure later in life. Our mutual interest in this topic led to the submission of a grant (with me and John as Chief Investigators) that was funded by the National Health and Medical Research Council of Australia (NHMRC; which is equivalent to the NIH in the United States and the MRC in the United Kingdom). From there our collaboration has continued to flourish for more than two decades and it is ongoing. We have been Chief investigators on another two NHMRC grants and have coauthored many papers. My research interests have diversified as a result of my collaboration with John and now my research is centered on both the cardiovascular system and the kidneys, with recent research clearly demonstrating that the two are inextricably linked. John Bertram was appointed as Head (Chair) of the Department of Anatomy at Monash University in 1998 (at the time he was one of the youngest Chairs of a department to be appointed to Monash University). In the first article of this Special Issue (Bertram, 2020), John describes how his career as department Chair unfolded. His article provides a personal perspective and insight into the challenges of chairing a university department and how the Department of Anatomy at Monash University more than tripled in size during his leadership and underwent a metamorphosis from the Department of Anatomy to the Department of Anatomy and Cell Biology to the Department of Anatomy and Developmental Biology, as it is known today. Under his leadership, the department grew from one of the smallest in the Faculty of Medicine at Monash University to one of the largest in the faculty, with a concomitant surge in research profile (output and quality). John was instrumental in developing the research profile within the department and this was brought about by the strategic recruitment of strong research groups with established international profiles. This was accompanied and facilitated by the building of state-of-the-art research facilities, of which John played a key role in the design. As a university department, the research groups recruited to the department are quite diverse; this has led to a dynamic research environment. I know from first-hand experience how these interactions help to broaden one's research perspective and help you to think outside the square; very successful collaborations have been developed in this way. Whilst Chair of the department, John played a key role in the mentoring of young scientists, both within his own research group and within the department in general. In reading his curriculum vitae, it is astounding to read that he has supervised 33 PhD students to completion (many as the main supervisor); he has also supervised 43 Honours projects (in Australia high-achieving students have the opportunity to conduct an Honours year at the end of their Bachelor Degree to conduct a year in research). In addition to his own students, John has played a key role in mentoring all Honours, Masters, and PhD students within the department and he has always led by example and exuded a passion for research. The Guest Editor, Megan Sutherland, was one of these students. Megan conducted her Honours project and PhD within my research group and given that her research was kidney-based, she also worked closely with John. John is a coauthor on many of Megan's publications and Megan now a successful early career researcher in her own right, continues to collaborate with John today, both in research and professionally; Megan recently convened a Satellite Meeting of the International Developmental Origins of Health and Disease (DOHaD) World Congress in Melbourne, which John chaired. Although the Department of Anatomy and Developmental Biology at Monash University now encompasses a wide variety of research areas, kidney research continues to remain strong. When John stepped down as Chair in 2016, there were five kidney research groups in the department (Bertram, Black, Li, Ricardo, and Smyth). All were recruited to the department during John's tenure as Chair and all have contributed to this Special Issue; an additional new renal research group has recently commenced in our department thus ensuring that renal research will continue to thrive into the future. Given the strong contribution John has made in renal research, it is only fitting that this Special Issue in The Anatomical Record in honor of John Bertram be devoted to kidney development and disease. John is world-renowned for his research relating to nephron endowment in human kidneys. His landmark studies, along with collaborators Wendy Hoy and Mike Hughson have been instrumental in identifying the wide range in nephron endowment in the human population (Hoy et al., 2003, 2006). Hughson, Farris III, Douglas-Denton, Hoy, & Bertram, 2003; Hughson et al. 2006; McNamara et al., 2008; Bertram, Douglas-Denton, Diouf, Hughson, & Hoy, 2011; Luyckx et al., 2013; Kanzaki et al., 2017). These findings have far-reaching clinical implications, based on Barry Brenner's early research linking people with kidneys at the lower end of the nephron number distribution with vulnerability to the development of hypertension and renal disease (Brenner & Anderson, 1992; Brenner, Garcia, & Anderson, 1988); Barry Brenner along with his long-term colleague Valerie Luyckx are authors in this Special Issue (Luyckx & Brenner, 2020). Many of John's studies, including the analyses of nephron number, involve meticulous stereological analyses. John is internationally renowned for his stereology expertise and was President of the International Society of Stereology for a number of years. Despite all the advances in microscopy and image analysis over recent years, unbiased stereological techniques are still considered a gold standard for the quantification of morphological parameters in three dimensions, and they are employed in verifying new renal imaging technologies. Indeed, it is John's expertise in stereology that has led to many of his collaborations over his career (Figure 2). Most of the articles that John has published in The Anatomical Record relate to stereological methods and their applications in the biological context (Bertram, Young, Spencer, & Gordon, 2000; Brandon et al., 2008; Foster, Bertram, & Holbrook, 1988; Nurcombe, Wreford, & Bertram, 1991; O'Connell et al., 2006). At The Anatomical Record, the strength of stereological methods in quantitating morphological biological parameters is well recognized and many of the leaders in the stereological field choose to publish in The Anatomical Record on a regular basis. John first published in The Anatomical Record in 1988, an article describing morphometric analyses in the human epidermis (Foster et al., 1988), and in 1991, he published a stereological study examining the total number of neurons in the developing chick lateral motor column (Nurcombe et al., 1991). Since then, he has published several other articles relating to stereological applications in the kidney (Akison et al., 2020; Bertram et al., 2000; Brandon et al., 2008; Concalves et al., 2020; David et al., 2010; Hughson, Hoy, & Bertram, 2020; O'Connell et al., 2006). In this Special Issue, Megan Sutherland, Danica Vojisavljevic, and I have written a step-by-step guide to stereological analyses of glomeruli that we routinely use in our laboratories (Sutherland, Vojisavljevic, & Black, 2020); these techniques we have developed in close collaboration with John Bertram and the members of his research group. John's close colleague Jens Nyengaard, also internationally recognized for his expertise in stereology and a regular contributor to The Anatomical Record, has also contributed an article to this Special Issue (Nielsen et al., 2020). In order to keep abreast of the latest research, John clearly sees the importance of embracing new technologies; an attitude also adopted by The Anatomical Record (the introduction of the WOW video articles reflects this). In this regard, John has been instrumental in developing state-of-the-art research platforms at Monash University, which have played a key role in attracting researchers to Monash University and to the Department of Anatomy and Development Biology. Importantly, over recent years John has been actively involved in developing image-based technologies in the kidney that can be used as an alternative to stereology. Along with his collaborators Norbert Gretz and Kevin Bennett, John has been exploring alternative techniques utilizing contemporary magnetic resonance imaging to quantitate the number and size of nephrons in the kidneys (Beeman et al., 2011; Beeman et al., 2014; Bennett, Bertram, Beeman, & Gretz, 2013; Bertram et al., 2013; Geraci et al., 2017; Heilmann et al., 2012). The development of these techniques has the potential to make a big impact on the fields of renal biology and clinical medicine, especially as accurate in vivo techniques are developed. Recent advances in these methodologies, feature highly in this Special Issue, with contributions from Norbert Gretz (Brenna et al., 2020), Kevin Bennett (Parvin, Charlton, Baldelomar, Derakhshan, & Bennett, 2020), and Jens Nyengaard (Nielsen et al., 2020) specifically relating to contemporary kidney imaging and quantitation. This Special Issue (comprised of eight original journal articles and 12 review articles) features studies relating to four key themes in renal research that John Bertram has been passionate about throughout his career: (a) renal anatomy, physiology, and pathology; (b) kidney development, podocyte biology, and applications of renal stem cells; (c) renal developmental programming, and (d) contemporary methodologies in renal research. An introduction to these themes and how John's research has directly contributed to these areas of renal research are described by Guest Editor, Megan Sutherland, in the Introduction of this Special Issue. All contributors to this issue have been colleagues and/or collaborated with John at some stage during their careers; a number of the articles are from former PhD students or junior colleagues whom John has mentored. All authors were delighted to be invited to contribute to this Special Issue in honor of John Bertram and together we celebrate his outstanding contributions to the Department of Anatomy and Developmental Biology at Monash University and to renal research!

New Findings What is the central question of this study? What is the immediate impact of moderate preterm birth on the structure and function of major conduit arteries using a pre‐clinical sheep model? What is the main finding and its importance? Postnatal changes in conduit arteries, including a significant decrease in collagen within the thoracic aortic wall (predominately males), narrowed carotid arteries, reduced aortic systolic blood flow, and upregulation of the mRNA expression of cell adhesion and inflammatory markers at 2 days of age in preterm lambs compared to controls, may increase the risk of cardiovascular impairment in later life. AbstractThe aim of this work was to compare the structure and function of the conduit arteries of moderately preterm and term‐born lambs and to determine whether vascular injury‐associated genes were upregulated. Time‐mated ewes were induced to deliver either preterm (132 ± 1 days of gestation; n = 11 females and n = 10 males) or at term (147 ± 1 days of gestation; n = 10 females and n = 5 males). Two days after birth, ultrasound imaging of the proximal ascending aorta, main, right and left pulmonary arteries, and right and left common carotid arteries was conducted in anaesthetized lambs. Lambs were then killed and segments of the thoracic aorta and left common carotid artery were either snap frozen for real‐time PCR analyses or immersion‐fixed for histological quantification of collagen, smooth muscle and elastin within the medial layer. Overall there were few differences in vascular structure between moderately preterm and term lambs. However, there was a significant decrease in the proportion of collagen within the thoracic aortic wall (predominantly in males), narrowing of the common carotid arteries and a reduction in peak aortic systolic blood flow in preterm lambs. In addition, there was increased mRNA expression of the cell adhesion marker P‐selectin in the thoracic aortic wall and the pro‐inflammatory marker IL‐1β in the left common carotid artery in preterm lambs, suggestive of postnatal vascular injury. Early postnatal differences in the function and structure of conduit arteries and evidence of vascular injury in moderately preterm offspring may place them at greater risk of cardiovascular impairment later in life.

The evaluation of a range of measures in the kidneys, such as developmental stage, rate and success, injury, and disease processes, relies on obtaining information on the three-dimensional structure of the renal corpuscles, and in particular the glomerular capillary tufts. To do this in the most accurate, comprehensive, and unbiased manner depends on a knowledge of stereological methods. In this article, we provide a practical guide for researchers on how to quantitate a number of structures in the kidneys, including the estimation of total glomerular number, glomerular capillary length and filtration surface area, and the cellular composition of individual glomeruli. Guidance is also provided on how to apply these methods to kidneys at different sizes and levels of maturity.

Disturbed fetal haemodynamics often affects cardiac development and leads to congenital cardiac defects. Reduced left ventricular (LV) preload in the fetus may result in hypoplastic LV, mitral and aortic valve, mimicking a moderate form of hypoplastic left heart complex. We aimed to induce LV hypoplasia by occluding the foramen ovale (FO) to reduce LV preload in the fetal sheep heart, using percutaneous trans-hepatic catheterisation. Under maternal anaesthesia and ultrasound guidance, hepatic venous puncture was performed in six fetal lambs (0.7–0.75 gestation). A coronary guidewire was advanced into the fetal inferior vena cava, right and left atrium. A self-expandable stent was positioned across the FO. An Amplatzer Duct Occluder was anchored within the stent for FO occlusion. Euthanasia and post-mortem examination was performed after 3 weeks. Nine fetuses were used as age-matched controls. Morphometric measurements and cardiac histopathology were performed. Compared with controls, fetal hearts with occluded FO had smaller LV chamber, smaller mitral and aortic valves, lower LV-to-RV ratio in ventricular weight and wall volume, and lower number of LV cardiomyocyte nuclei. We conclude that fetal FO occlusion leads to a phenotype simulating LV hypoplasia. This large animal model may be useful for understanding and devising therapies for LV hypoplasia.

BackgroundPreterm birth (< 37 weeks of gestation) occurs in approximately 10% of births worldwide; the majority of preterm births are moderately preterm (between 32 and 36 weeks gestation). We hypothesized that when birth occurs before term the major conduit arteries would be structurally and functionally immature and thus ill‐prepared for the hemodynamic transition that necessarily occurs at birth. Utilising a preclinical sheep model, our aims were to compare the structure and function of the thoracic aorta and common carotid arteries of moderately preterm (0.9 of gestation) and term‐born lambs in the immediate period after birth, and to determine whether there was upregulation of vascular injury‐associated genes following moderate preterm birth.MethodsTime‐mated ewes were induced to vaginally deliver lambs either preterm (132 ± 1 days of gestation; n=11 females and n=10 males) or at term (147 ± 1 days of gestation; n=10 females and n=5 males). At 2 days after birth, ultrasound imaging of the proximal ascending aorta, main, right and left pulmonary arteries and right and left common carotid arteries was conducted in anaesthetised lambs. The lambs were then euthanized and segments of the thoracic aorta and left common carotid artery were either snap frozen for later real‐time PCR analyses or immersion‐fixed in 10% buffered formalin for histological quantification of collagen, smooth muscle and elastin within the medial layer.ResultsOverall there were few differences in vascular structure, wall composition and blood flow measurements of large conduit arteries at postnatal day 2 between moderately preterm and term lambs. However, there was a significant decrease in the proportion of collagen within the thoracic aortic wall (predominantly in males; p=0.048), narrowing of the carotid arteries (p=0.004) and a reduction in peak aortic systolic blood flow (p=0.049); all of which have the potential to impact on cardiovascular function if they persist long‐term. In addition, there was significantly increased mRNA expression of the cell adhesion marker P‐selectin in the thoracic aortic wall (p=0.001) and the pro‐inflammatory marker IL‐1β in the left carotid artery (p=0.04) in preterm lambs, suggestive of postnatal vascular injury.ConclusionsThe findings suggest that offspring born moderately preterm may be at increased risk of cardiovascular impairment later in life.Support or Funding InformationThis study was funded by the National Health and Medical Research Council of AustraliaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

ABSTRACT Capillarization plays a key role in the growth of the developing heart. We therefore hypothesized that impaired heart development following intrauterine growth restriction (IUGR) may arise from inadequate myocardial capillary growth. The aims of the study were to examine the effect of IUGR on the growth and diffusion radius of intramyocardial capillaries in rats at postnatal day 1. Uteroplacental insufficiency was induced in rats in late gestation (E18, term = E22) by bilateral uterine artery and vein ligation (restricted offspring N = 12; six males and six females); offspring from sham‐operated dams were used as controls (N = 10; five males and five females). At postnatal day 1, the hearts were immersion‐fixed and heart volume, capillary length density, capillary diffusion radius, and total capillary length were stereologically determined. Restricted offspring were significantly smaller at birth, with a concomitant reduction in heart volume and total myocardial capillary length compared to controls. Capillary growth was not impaired relative to heart size, with no significant differences in capillary length density or diffusion radius in the myocardium of restricted and control offspring. There were no sex differences in any of the parameters examined. In conclusion, there was no evidence to indicate that microvascular development is compromised in the heart of IUGR offspring at 1 day after birth. Total myocardial capillary length, however, was significantly reduced in the growth restricted offspring and further longitudinal studies are required to elucidate the long‐term impact, particularly following hypertrophic cardiac growth. Anat Rec, 302:1580–1586, 2019. © 2018 American Association for Anatomy

Abstract Aims The worldwide prevalence of gestational diabetes mellitus (GDM) is increasing. Studies in rodent models indicate that hyperglycaemia during pregnancy alters kidney development, yet few studies have examined if this is so in humans. The objective of this study was to evaluate the association of treated GDM with foetal kidney size. Materials and Methods Participants were recruited from an Australian tertiary hospital, and clinical data were collected from women without GDM and women diagnosed and treated for GDM and their offspring. Participants underwent an obstetric ultrasound at 32‐34 weeks gestation for foetal biometry and foetal kidney volume measurement. Results Sixty‐four non‐GDM and 64 GDM women participated in the study. Thirty percent of GDM women were diagnosed with fasting hyperglycaemia, while 89% had an elevated 2‐hour glucose level. Maternal age, weight and body mass index were similar in women with and without GDM. Estimated foetal weight, foetal kidney dimensions, total foetal kidney volume and birth weight were similar in offspring of women with and without GDM. Conclusions We conclude that a period of mild hyperglycaemia prior to diagnosis of GDM and treatment initiation, which coincides with a period of rapid nephron formation and kidney growth, does not alter kidney size at 32‐34 weeks gestation.