Kidney growth following preterm birth: evaluation with renal parenchyma ultrasonography.

BACKGROUND: Preterm birth impairs nephrogenesis, leading to a reduced nephron endowment which is inextricably linked to hypertension and chronic kidney disease in adults. The aim of this study was to compare nephron endowment between preterm infants to that of intrauterine fetuses at the same gestational age (GA) using a novel indirect ultrasound measurement of the renal parenchymal thickness. We hypothesized that extrauterine and intrauterine renal parenchymal thickness would differ based on altered renal growth environments. METHODS: In this observational study, appropriately grown preterm infants (birth weight of between the 5th and 95th percentile) born <32 weeks, admitted to the neonatal department were eligible to participate. Renal parenchymal thickness of the infants was measured at 32- and 37-weeks postmenstrual age (PMA). These measurements were compared to the intrauterine renal parenchymal thickness of appropriately grown fetuses (control). RESULTS: At 32-weeks PMA, the preterm infants had a significantly thinner renal parenchyma compared to fetuses at 32-weeks GA suggesting they had less nephrons, however by 37-weeks there was no significant difference in renal parenchymal thickness. CONCLUSIONS: We propose that the differences in the extrauterine growth of the renal parenchyma in preterm infants may be due to a reduced number of nephrons and compensatory hyperfiltration. IMPACT: This article provides insight into the effects of prematurity on nephrogenesis by comparing extrauterine renal parenchymal growth of born preterm infants to the ideal intrauterine fetal growth. Renal parenchyma thickness measurement using ultrasonography is a novel non-invasive measurement of renal development for the determination of nephron endowment. Differences in the renal parenchymal thickness of the preterm infants may be due to a deficit in nephron number and compensatory hyperfiltration.

Optimization of a non-activating medium for short-term chilled storage of barramundi (Lates calcarifer) testicular spermatozoa.

Reliable short-term chilled sperm storage is a critical prerequisite to using advanced reproductive techniques for captive breeding of barramundi (Asian sea bass; Lates calcarifer). Marine Ringer's solution (MRS) is a common non-activating medium (NAM) and has previously been used to store sperm from wild-caught barramundi. However, MRS-stored spermatozoa from captive-bred barramundi were observed to lyse within 30 min incubation. Therefore, this study aimed to optimize the composition of NAM for short-term chilled storage by characterizing and mimicking the biochemical profile of seminal and blood plasma of captive-bred barramundi. To further understand the effect of each component, osmolality was first examined to determine its effect on sperm viability. Thereafter, the effects of NaHCO3, pH, and Na+ and K+ concentrations on sperm motility were investigated. Optimization of the NAM formula was achieved through iterative adaptions. The increase in NAM osmolality from 260 to 400 mOsm/kg led to a significant improvement in sperm viability. Moreover, using HEPES instead of NaHCO3 as buffering agent significantly enhanced sperm motility and velocity. As a result, sperm samples diluted with optimized NAM (185 mM NaCl, 5.1 mM KCl, 1.6 mM CaCl2·2H2O, 1.1 mM MgSO4·7H2O, 10.0 mM HEPES, 5.6 mM D+ glucose, 400 mOsm/kg, pH 7.4) and stored at 4 °C showed no significant loss in total motility for up to 48 h and retained progressive motility for up to 72 h. The optimized NAM developed in this study significantly extended the functional lifespan of spermatozoa during chilled storage, permitting the ongoing development of advanced reproductive technologies for barramundi.

The bacterial gut microbiome of probiotic-treated very-preterm infants: changes from admission to discharge.

BACKGROUND: Preterm birth is associated with the development of acute and chronic disease, potentially, through the disruption of normal gut microbiome development. Probiotics may correct for microbial imbalances and mitigate disease risk. Here, we used amplicon sequencing to characterise the gut microbiome of probiotic-treated premature infants. We aimed to identify and understand variation in bacterial gut flora from admission to discharge and in association with clinical variables. METHODS: Infants born <32 weeks gestation and <1500 g, and who received probiotic treatment, were recruited in North Queensland Australia. Meconium and faecal samples were collected at admission and discharge. All samples underwent 16S rRNA short amplicon sequencing, and subsequently, a combination of univariate and multivariate analyses. RESULTS: 71 admission and 63 discharge samples were collected. Univariate analyses showed significant changes in the gut flora from admission to discharge. Mixed-effects modelling showed significantly lower alpha diversity in infants diagnosed with either sepsis or retinopathy of prematurity (ROP) and those fed formula. In addition, chorioamnionitis, preeclampsia, sepsis, necrotising enterocolitis and ROP were also all associated with the differential abundance of several taxa. CONCLUSIONS: The lower microbial diversity seen in infants with diagnosed disorders or formula-fed, as well as differing abundances of several taxa across multiple variables, highlights the role of the microbiome in the development of health and disease. This study supports the need for promoting healthy microbiome development in preterm neonates. IMPACT: Low diversity and differing taxonomic abundances in preterm gut microbiota demonstrated in formula-fed infants and those identified with postnatal conditions, as well as differences in taxonomy associated with preeclampsia and chorioamnionitis, reinforcing the association of the microbiome composition changes due to maternal and infant disease. The largest study exploring an association between the preterm infant microbiome and ROP. A novel association between the preterm infant gut microbiome and preeclampsia in a unique cohort of very-premature probiotic-supplemented infants.

Exploring the long-term colonisation and persistence of probiotic-prophylaxis species on the gut microbiome of preterm infants: a pilot study.

Preterm infants suffer from a higher incidence of acute diseases such as necrotising enterocolitis and sepsis. This risk can be mitigated through probiotic prophylaxis during admission. This reduction in risk is likely the result of acute modulation of the gut microbiome induced by probiotic species, which has been observed to occur up until discharge. We aimed to determine if this modulation, and the associated probiotic species, persisted beyond discharge. We conducted both a cross-sectional analysis (n = 18), at ~ 18 months of age, and a longitudinal analysis (n = 6), from admission to 18 months of the gut microbiome of preterm infants using both shotgun metagenomics and 16S rRNA profiling respectively. The 16S amplicon sequencing revealed that the microbial composition of the probiotic-supplemented infants changed dramatically over time, stabilising at discharge. However, species from the probiotic Infloran®, as well as positive modulatory effects previously associated with supplementation, do not appear to persist beyond discharge and once prophylaxis has stopped.    Conclusions: Although differences exist between supplemented and non-supplemented groups, the implications of these differences remain unclear. Additionally, despite a lack of long-term colonisation, the presence of probiotics during early neonatal life may still have modulatory effects on the microbiome assembly and immune system training. What is Known: • Evidence suggests modulation of the microbiome occurs during probiotic prophylaxis, which may support key taxa that exert positive immunological benefits. • Some evidence suggests that this modulation can persist post-prophylaxis. What is New: • We present support for long-term modulation in association with probiotic prophylaxis in a cohort of infants from North Queensland Australia. • We also observed limited persistence of the probiotic species post-discharge.

Cystatin C: A more reliable biomarker of renal function in young infants? A longitudinal cohort study.

AIM: We carried out a longitudinal cohort study to measure serial CysC (Cystatin C) in a cohort of neonates born preterm until the age of 2 years. We hypothesised that CysC levels are independent of body weight and would not vary with gestational age. METHODS: This prospective cohort study was conducted from August 2014 until October 2016, and follow-up was completed in October 2018. Preterm infants at less than 28 weeks of gestation (extremely preterm infants) were recruited and followed up until the age of 24 months. Blood samples for measurement of CysC were collected at regular intervals. RESULTS: We recruited 58 preterm neonates with mean gestation was 26.2 (1.5) weeks, and a mean birth weight was 917 (140) g. One-way analysis of variance (ANOVA) did not show any significant difference in CysC levels between 28, 32 and 37 weeks' gestation (P = .09) despite a significant increase in body weight (P < .001). The mean CysC level was higher in the neonatal period and subsequently plateaued by 24 months. CONCLUSION: Serum CysC level is independent of body weight and not influenced by postnatal age nor by gender.

Is peripartum maternal fever alone a reliable predictor of neonatal sepsis? A single-centre, retrospective cohort study.

AIM: To determine the incidence rate of early-onset neonatal sepsis (EONS) among term neonates (gestation greater than 37 weeks) admitted to the neonatal intensive care unit for suspected sepsis and the association of EONS with maternal fever (temperature greater than 38°C). METHODS: A single-centre retrospective cohort study of all term neonates (gestation >37 weeks) admitted to and treated in the neonatal unit at the Townsville University Hospital between March 2015 and March 2020. Neonatal sepsis was confirmed with positive neonatal blood culture. Data on neonatal birth/stay and maternal pregnancy were collected from the electronic medical records and neonatal database. RESULTS: Data from 737 neonates who were admitted for treatment of EONS were analysed. Sixty % (426) reported maternal intrapartum fever, with 1.1% (5) of neonates developing blood culture-proven sepsis. Forty % did not report intrapartum fever (311), with 3% (9) of neonates developing sepsis. As such, the sensitivity and specificity of maternal fever are 1.14% and 97%, respectively. The positive predictive value was 35.7%, and the negative predictive value was 40.1%. Fourteen neonates developed EONS, and all of them were symptomatic. Seventy-eight % (334/426) of the women in the febrile group received epidural analgesia compared to 5% (16/311) in the afebrile group. Of the 95 neonates born to women with chorioamnionitis, one (1.0%) of the neonates born to women with chorioamnionitis developed sepsis. CONCLUSIONS: Intrapartum maternal fever is an unreliable predictor for EONS and leads to unnecessary antibiotic treatment. Symptoms in the neonate are a more reliable indicator of an ill neonate with blood culture-proven sepsis.

An evaluation of preterm kidney size and function over the first two years of life.

BACKGROUND: We carried out a study to determine the impact of prematurity on kidney development in the first 2 years of life. METHODS: In this prospective study, extremely preterm neonates (gestation < 28 weeks) were recruited and underwent assessments at 6, 12, and 24 months of age. A cohort of neonates born term were also recruited and followed up for 24 months. The primary outcomes measured in this study were total kidney volume (TKV) and estimated glomerular filtration rate (eGFR); albuminuria and blood pressure measurements (all provided as mean (standard deviation)) were the secondary outcomes. RESULTS: Fifty-three premature and 31 term neonates (control) were recruited. At the age of 24 months (corrected age), infants born preterm had significantly smaller TKV (56.1 (9.4) vs. 64.8 (10.2) mL; P = 0.006). There was no difference in eGFR. These preterm infants were smaller (11.25 (1.53) vs. 12.9 (1.8) kg; P = 0.002) and shorter (83.8 (3.0) vs. 86.3 (3.4) cm; P = 0.02) when compared with the control group. At 6, 12, and 18 months respectively, preterm infants had, relative to their height, significantly smaller kidney volumes (0.54 (0.1) vs. 0.59 (0.1) mL/cm, P = 0.05; 0.61 (0.1) vs.0.71 (0.1) mL/cm, P = 0.003; and 0.67 (0.1) vs.0.76 (0.1) mL/cm, P = 0.006). CONCLUSIONS: Relative to body length, TKV in premature infants is smaller. Since length reflects adult body proportions more accurately than BSA, TKV to height ratio may be a more important measure in the child. Despite smaller TKV (and therefore fewer nephrons), infants born prematurely achieve similar eGFRs in the first 24 months of life, probably due to single-nephron hyperfiltration.

Fetal kidney charts of a novel measurement of the renal parenchymal thickness to evaluate fetal kidney growth and potential function.

OBJECTIVE: The objective of this study was to develop new standard growth charts for fetal renal parenchymal thickness, length, and volume to define normal ranges for use in clinical practice and to assess the reliability of these measurements. METHODS: This was a prospective, longitudinal study of 72 low-risk singleton pregnancies undergoing serial ultrasound examinations at least every four weeks. Multiple renal measurements were performed on both kidneys at each scan. The renal parenchymal thickness was measured in the mid-sagittal plane. Standard charts were developed and the intra and interobserver reliability for the renal measurements was analysed. RESULTS: Standard charts were developed for fetal renal parenchymal thickness, length, and volume. CONCLUSION: We present novel charts, which demonstrate the growth of the fetal renal parenchyma during pregnancy. They will be useful in clinical practice to identify any alterations from these normal ranges, which may be an important criterion for assisting prenatal diagnosis of renal pathologies and future studies in the prediction of kidney function.

Retinal microvascular development in the first two years.

The link between in utero and early life insults and the development of chronic illness remains to be fully understood, but there is increasing data to indicate that microvasculature pathology plays an important mechanistic role. Currently available data indicate that retinal microvasculature changes are detectable in children as young as six years of age, however, there are no data for younger children. We present retinal microvasculature measurement from the first two years of life. Retinal images suitable for analysis were available from 18 infants in our proof-of-concept study. The mean and standard deviation (SD) for birth weight and gestation was 3410 (384) g and 39.1(1.4) weeks, respectively. Retinal vessel calibres were summarized as the mean(SD) central retinal arteriolar equivalent (CRAE) at six months of age was 156 (32) µm, increased to 175 (75) µm by 12 months and a slightly declined by 24 months of age to 168 (50) µm. In a similar pattern, mean(SD) central retinal venular equivalent (CRVE) at six months was 211 (19) µm, increased to 238 (25) µm by 12 months of age followed by a slight decline at 24 months of age to 222 (36) µm. The arterio-venous ratio and tortuosity index remained the same at 6, 12 and 24 months. Findings from this study could help future investigators better understand early microvasculature changes and adaptation that occur early in life.

Female preterm indigenous Australian infants have lower renal volumes than males: A predisposing factor for end-stage renal disease?

AIM: Indigenous Australians have an increased risk of developing chronic kidney disease (CKD). Indigenous women have a higher rate of CKD than men. In a cohort of Indigenous and non-Indigenous preterm neonates, we assessed total renal volume (TRV) (a proxy indicator for nephron number). We hypothesized that there would be no difference in renal volume between these two groups at term corrected (37 weeks gestation). METHODS: Normally grown preterm neonates less than 32 weeks of gestation were recruited and at term corrected dates, the neonates underwent renal ultrasonography (TRV measurements), urine microalbumin-creatinine ratio and serum analysis for Cystatin C measurement for estimated glomerular filtration rate (eGFR) calculation. RESULTS: One hundred and five neonates (38 Indigenous; 67 non-Indigenous) were recruited. Indigenous neonates were significantly more premature and of lower birth weight. At term corrected age, Indigenous neonates had a significantly smaller TRV (18.5 (4.2) vs 21.4 (5.1) cm3 ; P = 0.027) despite no significant difference in body weight. Despite having a smaller TRV, there was no significant difference in eGFR between Indigenous and Non-indigenous neonates (47.8 [43.2-50.4] vs 46.2 [42.6-53.3] ml/min per 1.73 m2 ; P = 0.986). These infants achieve similar eGFR through hyperfiltration, which likely increases their future risk of CKD. There was no difference in microalbumin-creatinine ratio. Female Indigenous neonates, however, had significantly smaller TRV compared with Indigenous male neonates (15.9 (3.6) vs 20.6 (3.6) cm3 ; P = 0.006), despite no difference in eGFR, birth weight, gestational age, and weight at term corrected. CONCLUSION: The difference in TRV is likely to be an important risk factor for the difference in morbidity and mortality from renal disease reported between male and female Indigenous adults.

Significance of Anti-Myosin Antibody Formation in Patients With Myocardial Infarction: A Prospective Observational Study.

BACKGROUND: Anti-myosin antibodies (AMAs) are often formed in response to myocardial infarction (MI) and have been implicated in maladaptive cardiac remodelling. We aimed to: (1) compare AMA formation in patients with Non-ST-Elevation MI (NSTEMI) and ST-Elevation MI (STEMI); (2) evaluate factors predicting autoantibody formation; and, (3) explore their functional significance. METHODS: Immunoglobulin M (IgM) and Immunoglobulin G (IgG) AMA titres were determined in serum samples collected at admission, 3 and 6 months post MI. The relationship between demographic and clinical data, and antibody formation, was investigated to determine factors predicting antibody formation and functional significance. RESULTS: Forty-three (43) patients were consecutively recruited; 74.4% were positive for IgM at admission, compared with 23.3% for IgG. Mean IgG levels increased by 1.24% (±0.28) at 3 months, and 13.55% (±0.13) at 6 months post MI. Mean antibody levels were significantly higher in the NSTEMI cohort at both follow-up time points for IgG (p<0.001, p<0.0001), but not IgM (p=0.910, p=0.066). A moderately positive correlation between infarct size and increase in mean IgM concentration was observed at 3 months (r(98)=0.455; p=0.015). Anti-myosin antibody formation was not associated with an unfavourable outcome at follow-up. CONCLUSIONS: Anti-myosin antibodies are formed in a significant proportion of patients following MI, particularly among those with NSTEMI. While IgM levels fall after infarction, IgG levels increase and persist beyond 6 months of follow-up. This raises the possibility that they may contribute to long-term myocardial damage and dysfunction. Future research should focus on the specific epitopes that are targeted by these antibodies, and their functional significance. This may result in the emergence of novel therapies to attenuate cardiac dysfunction in MI patients.

Extra uterine development of preterm kidneys.

OBJECTIVE: We carried out a study to determine the impact of prematurity on renal development. The primary outcomes measured were nephrinuria and albuminuria; renal volume and glomerular filtration rate were the secondary outcomes. METHODS: Preterm neonates born at less than 28 weeks of gestation, with birth weight between 10th and 90th centile (appropriate for gestational age), were recruited and underwent assessments at 28, 32 and 37 weeks postmenstrual age (PMA). RESULTS: Fifty-three premature neonates and 31 term neonates (control) were recruited. The median gestational age of the premature neonates was 26.4 [24.7-27.4] weeks, with a mean birth weight of 886 (179) g. The mean gestational age of term neonates was 39.1 (1.2) weeks and the mean birth weight was 3406 (406) g. The median age of the term neonates was 6.5 [3.0-12.5] days. The total kidney volume (TKV) almost doubled from 10.3 (2.9) cm3 at 28 weeks PMA to 19.2 (3.7) cm3 at 37 weeks PMA (P = 0.0001). TKV at 37 weeks PMA was significantly smaller compared to term neonates (19.2 (3.7) vs 26.3 (7.0) cm3; P = 0.0001). However, there was no significant difference in estimated glomerular filtration rate (eGFR) between premature neonates (at 37 weeks PMA) and term neonates (control) (43.5 [39.7-48.9] vs. 42.0 [38.2-50.0] mL/min/1.73 m2; P = 0.75). There was a statistically significant decline in nephrin-creatinine ratio and albumin-creatinine ratio from 32 to 37 weeks PMA. CONCLUSIONS: Despite having a smaller renal volume (and fewer nephrons), extremely premature neonates achieve similar eGFRs at corrected term as term-born neonates, likely through single nephron hyperfiltration. Extremely premature neonates also show evidence of glomerular injury.

An ex vivo comparison of adenosine and lidocaine solution and University of Wisconsin solution for hypothermic machine perfusion of porcine kidneys: potential for development.

BACKGROUND: The optimal hypothermic machine perfusion (HMP) solution has not yet been developed. An adenosine and lidocaine (AL) solution has been shown to be protective in cardiac preservation. The aim of the present study was to examine a modified AL solution with low Ca2+, 16 mM Mg2+, and 4% albumin on kidney preservation compared with University Wisconsin solution (UW). METHODS: Twenty donation of organs after cardiac death porcine kidneys underwent HMP for 10 h (AL, n = 10; UW, n = 10) and then 2 h of normothermic reperfusion. Perfusion dynamics, functional parameters, histology, and real-time microdialysis were used to assess kidney responses and viability. RESULTS: During HMP, modified AL-perfused kidneys maintained higher flow rates (21.5 versus 17.9 mL/min/100 g, P = 0.01), with perfusion flow index during the first 3 h 25% greater than with UW (AL = 0.50 ± 0.2, UW = 0.40 ± 0.17 mL/min/100 g/mmHg; P = 0.03), followed by an increase in UW kidneys which was not significantly different to AL over the remaining 7 h (0.54 versus 0.55 mL/min/100 g/mmHg, respectively). During warm reperfusion, there were no significant differences between the two HMP groups in creatinine clearance, oxygen, and glucose consumption between groups. Modified AL kidneys had significantly lower perfusate lactates (3.1 versus 4.1 mmol/L, P = 0.04) during reperfusion and lower cortical lactate levels (AL = 0.66 ± 0.31, UW = 0.89 ± 0.53 mM, P = 0.33). Histology showed similar degrees of reperfusion injury. CONCLUSIONS: We conclude that HMP with modified AL solution showed improved perfusion compared with UW and lower perfusate lactate levels during warm reperfusion. Further modification of the AL composition is warranted and may lead to more rapid kidney stabilization and improved graft viability assessment, potentially expanding donor pools.

The Relationship between Maternal Smoking and Infant Birth Weight: Improving Accuracy through Urine Cotinine Analysis and Effective Medical Record Strategies.

OBJECTIVE: We conducted a study to determine if antenatally collected maternal urine cotinine (a metabolite of nicotine) measurements can be used to assess the neonatal impact of nicotine exposure during pregnancy. This was a prospective longitudinal cohort of mother-infant dyads. Only term singleton pregnancies were included. The primary outcome measure was the correlation between maternal urine cotinine and infant birth weight. METHODS: We analysed data from 238 mother-neonate dyads. Smoking habits were recorded during routine prenatal check-ups and urine samples were collected to measure cotinine and creatinine levels. RESULTS: Urine cotinine was detected in 50.4% (120/238) of women from the whole cohort, but only 16% (38/238) self-reported as smokers (chi-square 39.7, p < 0.0001), and these women had significantly smaller babies (p = 0.010). There was a significant negative correlation between maternal urine cotinine and birth weight (Spearman's coefficient = -0.0226, p = 0.013). Female babies born to women with nicotine in their urine were significantly smaller (p = 0.001). CONCLUSIONS: Infant birth weight significantly reduced in mothers with exposure to nicotine during pregnancy. The number of women exposed to nicotine during late pregnancy (measured in urine) was markedly higher than self-reported and national smoking percentages, suggesting an urgent need for an improvement in medical record reporting on smoking habits to better assess neonatal outcomes.

Urinary nephrin-a potential marker of early glomerular injury: a systematic review and meta-analysis.

BACKGROUND: Both early recognition of glomerular injury and diagnosis of renal injury remain important problems in clinical settings, and current diagnostic biomarkers have limitations. The aim of this review was to determine the diagnostic accuracy of urinary nephrin for detecting early glomerular injury. METHODS: A search was conducted through electronic databases for all relevant studies published until January 31, 2022. The methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled sensitivity, specificity, and other estimates of diagnostic accuracy were determined using a random effect model. The Summary Receiver Operating Characteristics (SROC) was used to pool the data and to estimate the area under the curve (AUC). RESULTS: The meta-analysis included 15 studies involving 1587 participants. Overall, the pooled sensitivity of urinary nephrin for detecting glomerular injury was 0.86 (95% CI 0.83-0.89) and specificity was 0.73 (95% CI 0.70-0.76). The AUC-SROC to summarise the diagnostic accuracy was 0.90. As a predictor of preeclampsia, urinary nephrin showed a sensitivity of 0.78 (95% CI 0.71-0.84) and specificity of 0.79 (95% CI 0.75-0.82), and as a predictor of nephropathy the sensitivity was 0.90 (95% CI 0.87-0.93), and specificity was 0.62 (95% CI 0.56-0.67). A subgroup analysis using ELISA as a method of diagnosis showed a sensitivity of 0.89 (95% CI 0.86-0.92), and a specificity of 0.72 (95% CI 0.69-0.75). CONCLUSION: Urinary nephrin may be a promising marker for the detection of early glomerular injury. ELISA assays appear to provide reasonable sensitivity and specificity. Once translated into clinical practice, urinary nephrin could provide an important addition to a panel of novel markers to help in the detection of acute and chronic renal injury.

The effects of ketogenic metabolic therapy on mental health and metabolic outcomes in schizophrenia and bipolar disorder: a randomized controlled clinical trial protocol.

Background: Schizophrenia, schizoaffective disorder, and bipolar affective disorder are debilitating psychiatric conditions characterized by a chronic pattern of emotional, behavioral, and cognitive disturbances. Shared psychopathology includes the pre-eminence of altered affective states, disorders of thoughts, and behavioral control. Additionally, those conditions share epidemiological traits, including significant cardiovascular, metabolic, infectious, and respiratory co-morbidities, resulting in reduced life expectancy of up to 25 years. Nutritional ketosis has been successfully used to treat a range of neurological disorders and preclinical data have convincingly shown potential for its use in animal models of psychotic disorders. More recent data from open clinical trials have pointed toward a dramatic reduction in psychotic, affective, and metabolic symptoms in both schizophrenia and bipolar affective disorder. Objectives: to investigate the effects of nutritional ketosis via a modified ketogenic diet (MKD) over 14 weeks in stable community patients with bipolar disorder, schizoaffective disorder, or schizophrenia. Design: A randomized placebo-controlled clinical trial of 100 non-hospitalized adult participants with a diagnosis of bipolar disorder, schizoaffective disorder, or schizophrenia who are capable of consenting and willing to change their diets. Intervention: Dietitian-led and medically supervised ketogenic diet compared to a diet following the Australian Guide to Healthy Eating for 14 weeks. Outcomes: The primary outcomes include psychiatric and cognitive measures, reported as symptom improvement and functional changes in the Positive and Negative Symptoms Scale (PANSS), Young Mania Rating Scale (YMS), Beck Depression Inventory (BDI), WHO Disability Schedule, Affect Lability Scale and the Cambridge Cognitive Battery. The secondary metabolic outcomes include changes in body weight, blood pressure, liver and kidney function tests, lipid profiles, and markers of insulin resistance. Ketone and glucose levels will be used to study the correlation between primary and secondary outcomes. Optional hair cortisol analysis will assess long-term stress and variations in fecal microbiome composition. Autonomic nervous system activity will be measured via wearable devices (OURA ring and EMBRACE wristband) in the form of skin conductance, oximetry, continuous pulse monitoring, respiratory rate, movement tracking, and sleep quality. Based on the encouraging results from established preclinical research, clinical data from other neurodevelopment disorders, and open trials in bipolar disorder and schizophrenia, we predict that the ketogenic metabolic therapy will be well tolerated and result in improved psychiatric and metabolic outcomes as well as global measures of social and community functioning. We additionally predict that a correlation may exist between the level of ketosis achieved and the metabolic, cognitive, and psychiatric outcomes in the intervention group.

Allostatic load and systemic comorbidities in psychiatric disorders.

Psychiatric disorders are complex, disabling, and chronic conditions that are often accompanied by one or more systemic medical comorbidities. In this narrative review, we provide an overview of the allostatic load concept, which represents a multi-system dysregulation in response to chronic stress and link it to systemic comorbidities associated with psychiatric disorders. We synthesized published literature gathered using Medline (Ovid), Scopus, and PsychInfo and identified a high frequency of systemic comorbidities for both mood and psychotic disorders. The identified cardiovascular, metabolic, and immune comorbidities may represent the result of chronic wear and tear caused by a complex interaction between chronic psychosocial stress, health risk behaviors, pharmacological stressors, and the biological systems involved in the development of allostatic load. These findings support the notion that psychiatric disorders should be re-conceptualized as systemic disorders, affecting the brain and systemic biological pathways in an interconnected fashion to result in systemic comorbidities. We suggest that the multi-systemic and multi-dimensional approach that drives the allostatic load concept should be considered for understanding comorbidities in vulnerable psychiatric patients.

Fetal renal artery blood flow - Normal ranges.

INTRODUCTION: The study objectives were to develop standard charts for fetal renal artery blood flow to define normal ranges and to assess the reliability of the measurements. METHODS: This prospective, longitudinal study reviewed 72 low-risk singleton pregnancies who had serial ultrasound examinations. Pulse wave Doppler was used to obtain the resistivity and pulsatility indices of the fetal renal arteries. Standard charts of the fetal renal arteries were created using mixed effects modelling and the intra- and interobserver reliability for the renal blood flow measurements was analysed. RESULTS: Standard charts of the normal ranges of the renal artery resistive index (RI) and pulsatility index (PI) of the fetal renal arteries were created. The 3rd, 5th, 10th, 50th, 90th, 95th and 97th centiles were calculated. The intraclass correlation coefficient was acceptable for intraobserver reliability (RI = 0.66, PI = 0.88) and poor for interobserver reliability (RI = 0.11, PI = -0.56). CONCLUSIONS: These novel charts demonstrate the change of the fetal renal artery blood flow during pregnancy. These may be used in clinical practice to detect variations from these normal ranges and be useful in future studies of kidney function projection.

Childhood adversity, allostatic load, and adult mental health: Study protocol using the Avon Longitudinal Study of Parents and Children birth cohort.

Introduction: The cumulative burden of chronic stress and life events has been termed allostatic load. Elevated allostatic load indices are associated with different mental health conditions in adulthood. To date, however, the association between elevated allostatic load in childhood and later development of mental health conditions has not been investigated. Methods: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we will calculate allostatic load indices using biomarkers representing the cardiovascular, metabolic, immune, and neuroendocrine systems, at the ages of 9 and 17 years. Bivariate and multivariable logistic regression models will be used to investigate the association between allostatic load and psychiatric disorders in adulthood. Furthermore, the role of adverse childhood experiences as a modifier will be investigated. Discussion: This protocol describes a strategy for investigating the association between elevated allostatic load indices in childhood at the age of 9 years old and psychiatric disorders in adulthood at 24 years old.