Introduction: Schizotypal traits (unusual perceptual experiences and cognitive-perceptual differences) and cyclothymic traits (mood instability and affective fluctuations) represent subclinical personality dimensions observed in non-clinical populations. Allostatic load (AL), reflecting cumulative multisystem physiological stress, may provide insight into biological processes associated with these traits. This study examined whether individuals with elevated schizotypy or cyclothymic traits show distinct AL-related biomarker patterns. Methods: Three groups were defined using validated psychometric measures: 30 individuals with schizotypy traits (PSF), 25 with cyclothymic traits (CF), and 30 control participants (CGs). Machine learning (ML) analyses included a Random Forest model with leave-one-subject-out cross-validation to examine differences in biomarker profiles between groups, and Shapley Additive exPlanations (SHAP) analysis was applied to determine the relative importance of biomarkers. The highest-ranking biomarkers were subsequently used to construct a reduced AL index. Results: Significant differences among groups were observed in oxidative stress system markers (p = 0.014). SHAP analysis identified creatinine, diastolic blood pressure, uric acid, and low-density lipids as key features for the CF group, and heart rate, TSH, uric acid, and glucose for the PSF group, with uric acid emerging as the strongest shared biomarker. A reduced biomarker panel selected using SHAP achieved subject-level classification accuracy of 63.6% (95% CI 50.9–76.4) and AUC of 0.625 (95% CI 0.469–0.768) and showed comparable performance to the full model. However, label-permutation testing yielded a borderline result (p = 0.055), indicating that these findings should be considered exploratory. The AL index derived from the top-ranked biomarkers was significantly lower in the CF than in the CG group (p = 0.007), whereas differences between the PSF and CG groups did not remain significant after correction. Findings are exploratory and require validation in an independent cohort. Conclusions: Distinct biomarker patterns associated with schizotypal and cyclothymic traits were identified in a non-clinical population, highlighting differences in stress-related physiological processes. ML-based feature-importance analysis identified a reduced set of biomarkers associated with trait-related biological profiles; however, these findings remain exploratory and require external validation.
BACKGROUND:Distinguishing pathological fetal growth restriction (FGR) from constitutionally small-for-gestational-age (SGA) fetuses remains clinically challenging. The maternal soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio reflects placental angiogenic imbalance and may assist recognition of placental insufficiency. OBJECTIVES:To assess the performance of the maternal sFlt-1/PlGF ratio for differentiating FGR from SGA and appropriate-for-gestational-age (AGA) pregnancies. SEARCH STRATEGY:PubMed, Scopus, Web of Science, Embase, Cochrane CENTRAL and Google Scholar were searched from inception to 14 January 2025 using MeSH and text terms for "sFlt-1", "PlGF", "fetal growth restriction", and "small-for-gestational-age". SELECTION CRITERIA:Peer-reviewed human studies reporting maternal sFlt-1/PlGF ratios in pregnancies classified as FGR, SGA or AGA. DATA COLLECTION AND ANALYSIS:Two reviewers independently screened records; one reviewer extracted data and assessed quality with second-reviewer verification (> 30%). Owing to heterogeneity, findings were synthesised narratively, with a meta-analysis restricted to studies directly comparing FGR and SGA. MAIN RESULTS:Forty observational studies (> 25 000 pregnancies) were included. Across gestation, FGR consistently showed higher sFlt-1/PlGF ratios than AGA. SGA exhibited modest or no elevation. Four studies (n = 614) enabled pooling: log-transformed ratios were significantly higher in FGR than SGA (SMD 0.58, 95% CI 0.35-0.81) with low heterogeneity. Ratios were most discriminatory in early-onset placental FGR. CONCLUSIONS:The sFlt-1/PlGF ratio is best considered an adjunctive indicator of placental insufficiency. Normal results can support expectant management in SGA when ultrasound and Doppler are reassuring, whereas elevated values warrant closer surveillance.
The pathophysiology of psychiatric disorders is complex and involves multiple biological systems. The allostatic load (AL) model offers a framework to capture this multisystem dysregulation by assessing biomarkers that reflect the activity of different physiological systems. This systematic review aimed to summarise current literature on the association between AL and psychiatric disorders. The databases Medline (Ovid), PsycINFO, Ovid Emcare, CINAHL, Cochrane, and Scopus were systematically searched from inception to July 2025. A total of twenty-eight studies were included in the systematic review, and sixteen were eligible for meta-analysis. We found that individuals with a psychiatric disorder demonstrated elevated AL compared to healthy controls (HCs). Furthermore, the meta-analyses revealed an overall standardised mean difference of the between-group meta-analysis, which demonstrated higher AL in individuals with schizophrenia and first-episode psychosis (SMD: 0.97; 95% CI: 0.76, 1.18; p < .0001) compared to HCs. In contrast, no significant difference in AL was observed for individuals with major depressive disorder (SMD: 0.07; 95% CI: -0.23; 0.37; p = 0.67). In conclusion, the AL model may offer a valuable tool for evaluating the impact of chronic stress across various biological systems. This approach can be applied to the early intervention of the core pathophysiology as well as systemic comorbidities that are common among those with psychiatric symptoms.
Introduction Adolescence is a stress-sensitive period for neurodevelopment and mental health, with chronic stress implicated in the onset of psychological disorders. Hair cortisol concentration (HCC) serves as a non-invasive biomarker of long-term hypothalamic-pituitary-adrenal (HPA) axis activity, yet its relevance to adolescent mental health remains inconsistently characterised. Methods This longitudinal study examined HCC in 302 community-dwelling adolescent twins from Brisbane, Australia, with data collected at two sessions approximately two years apart, following a standardised assessment protocol. Three cm long hair samples were analysed to quantify cumulative stress exposure over three months, and participants completed self-reported measures of depression, anxiety, daily stress, social support, and adverse childhood experiences (ACEs). Linear mixed-effects models and quantile regression were used to examine mean-level and distributional associations between HCC and psychological and environmental variables. Results Average HCC decreased significantly between sessions, with no main effect of sex, twin zygosity, or pubertal stage. In males, a higher average HCC at the second session was associated with elevated general anxiety, whereas in females, a higher average HCC was linked to higher exposure to severe lifetime stress. No associations were found between average HCC and ACEs. Conclusion These findings suggest that average HCC, reflecting cumulative cortisol secretion over the three months before each assessment, provides a stable measure of long-term cortisol in adolescents, although its associations with psychosocial stressors were limited in this cohort. Rather than functioning as a broadly sensitive biomarker of chronic stress, HCC may capture specific stress-related processes in certain subgroups, and its utility may depend on the type, timing, and chronicity of stress exposure.
BackgroundSchizophrenia, 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.Objectivesto 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.DesignA 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.InterventionDietitian-led and medically supervised ketogenic diet compared to a diet following the Australian Guide to Healthy Eating for 14 weeks.OutcomesThe 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.
BACKGROUND:Adolescence is a critical period for brain maturation, influenced by stress and hormonal changes. Chronic stress can lead to increased allostatic load (AL), a cumulative measure of multisystem dysregulation, and insulin resistance (IR), both of which are linked to mental health disorders. We hypothesized that heightened AL and IR during adolescence (age 17) would predict the emergence of mood and psychotic symptoms in young adults. METHODS:This study used data from the Avon Longitudinal Study of Parents and Children, a population cohort from Bristol, United Kingdom. RESULTS:Our results showed that elevated AL at age 17 was significantly associated with the development of mood disorder symptoms (MDS) and psychotic disorder symptoms (PDS) and the co-occurrence of mood and psychotic disorder symptoms (MPDS) at age 24 (p < 0.001). Mean AL increased progressively across these symptom groups, indicating a dose-response relationship between physiological dysregulation and mental health burden (MDS = 3.67, PDS = 3.89, and MPDS = 4.03). We also observed that IR was significantly elevated in the MDS, PDS, and MPDS groups compared to healthy controls (HCs). IR was most prevalent in the PDS group, suggesting a possible association between metabolic dysfunction and psychosis risk. CONCLUSION:This study demonstrated that multisystem dysregulation in late adolescence precedes the onset of mood and psychotic symptoms in early adulthood. These results support the use of AL and metabolic markers as early indicators of psychiatric vulnerability and highlight the potential for early intervention targeting systemic dysregulation to prevent the onset of mental health disorders.
Introduction:During pregnancy, placental microvasculature undergoes significant adaptations to support the developing fetus. However, studying placental microcirculation in vivo remains challenging. This study examined the potential of using retinal microvasculature measurements as a proxy, along with umbilical cord blood markers of angiogenesis and inflammation together with urine cotinine (a nicotine metabolite), to gain insights into the microvasculature changes in the human placenta. Methods:During the 24-month recruitment period (August 2019 to August 2021), the study was open to all pregnant women receiving antenatal care at Townsville University Hospital in Australia. Immediately after childbirth, the maternal central retinal artery equivalent (CRAE) diameter, the central retinal vein equivalent (CRVE) diameter, and the arteriovenous ratio (AVR) were determined using a handheld non-mydriatic retinal camera. Umbilical cord blood and maternal urine were also collected and analyzed. Results:Data from 80 women were analyzed. Multivariate analyses found a significant negative correlation between CRAE, CRVE, and tumor necrosis factor receptor 2 (TNFR2) and a significant positive correlation between CRVE and urine cotinine, the diagnosis of preeclampsia, and diabetes mellitus in pregnancy. Conclusions:We propose that the changes in the retinal artery and vein may reflect alterations in the placenta's spiral artery and its draining vein, with TNFR2 acting as a common mediator.
Introduction Allostatic load (AL), a cumulative measure of stress, has been implicated in the pathophysiology of major depressive disorder (MDD). However, the relationship between AL and depressive symptoms, treatment response, and metabolic health remains unclear. Methods This study investigated AL in unmedicated (>6 weeks) inpatients with MDD (n = 31) at baseline and after 6 weeks of treatment with either Venlafaxine or Mirtazapine. Baseline patients were compared to age- and sex-matched healthy controls. Depressive symptoms and functional status were assessed using the Hamilton Scale for Depression (HAMD) and Global Assessment of Functioning (GAF) rating scales. Furthermore, metabolic syndrome (MetS) was assessed in the MDD patients at baseline and Week 6. Result Our findings indicate that AL was significantly elevated in MDD patients compared to healthy controls (HCs; n = 31) at baseline (p = 0.031). AL was not associated with functional status at baseline or at Week 6. MetS was prevalent among MDD patients but was not correlated with clinical symptom severity. Lastly, AL significantly (p = 0.02) decreased after 6 weeks of antidepressant treatment, although the reduction was not predictive of symptom improvement or functional remission. Discussion/Conclusion These findings suggest that AL reflects underlying multisystem dysregulation in MDD rather than symptom severity or treatment responsiveness. The observed decrease in AL during treatment may indicate an effect of antidepressants, although further research with longer follow-up is needed. The observed potential sex difference in AL warrants further investigation using larger sample sets.
Barramundi (Asian sea bass, Lates calcarifer ) is a species with a mass-spawning reproductive strategy whereby adults synchronously release their gametes into the water column. In captivity, this reproductive strategy usually results in uneven paternal contributions to each cohort of progeny, creating skews in family size that hinder the effectiveness of selective breeding programs. As sperm quality influences fertilization success and early larval development, we investigated the relationship between sperm quality and spawning performance. Accordingly, we assessed three established breeding cohorts. Sperm samples ( n = 22) were collected by cannulation. Sperm motility was assessed using CASA, and sperm viability and DNA integrity were evaluated using dual-fluorescence stains by flow cytometry. Broodstock were induced to spawn across two consecutive nights, and offspring were collected at 2.5 h and 12 h post-fertilization (hpf) and 24 h and 48 h post-hatching (hph). Offspring were assessed for morphological abnormalities, and key morphological parameters were recorded. Offspring collected at 2.5 hpf and 24 hph were genotyped to determine their parentage and examine the relationship between sperm quality of individual males and offspring survival. Results highlighted that male condition factor (K) and sperm quality were highly variable within each breeding cohort. Males with a lower condition factor showed lower sperm motility and velocity. In contrast, males with a higher condition factor showed higher sperm motility and velocity but also higher levels of sperm DNA damage. While all males were capable of fertilization, males with a lower condition factor had greater paternal contribution. In this study, a reduction in skewed paternity was also found on Night 2 of spawning compared to Night 1. Moreover, males from Tank B, which had the lowest level of sperm DNA damage, had the most even paternal contribution. Conversely, highly skewed maternal contributions were reported across all spawning events. The results of this study suggest that additional complex dynamics and further unmeasured variables, such as spawning behavior, social hierarchy, and the spawning induction procedure, may also skew family sizes. Therefore, further development of artificial reproductive technology is recommended to gain greater control over individual contribution and overcome current breeding bottlenecks.
Introduction: Glomerular injury may occur during pregnancy as a consequence of systemic disease and pregnancy-related medical complications. While urinary nephrin has been shown to provide early identification of preeclampsia (PE) in high-risk pregnancies, the role of urinary nephrin in determining glomerular injury in pregnant women is yet to be explored. This study aimed to investigate the use of urinary nephrin as a predictor for early glomerular injury in a study conducted at the Townville University Hospital. Methods and Materials: A cross-sectional study was conducted. All pregnant women with a full dataset (n = 273) were classified into three categories according to their urinary albumin-to-creatinine ratio (ACR): normoalbuminuria, microalbuminuria and macroalbuminuria. Continuous variables were compared between groups, and the cut-off value for the urinary nephrin-to-creatinine ratio (NCR) was determined to predict albuminuria as an indirect indicator of early glomerular injury. The percentages of pregnant women who had elevated nephrinuria were calculated for each of the ACR categories. Results: Urinary NCR positively correlated with urinary ACR (r = 0.29, p < 0.0001). Urinary NCR increased comparably in women with normoalbuminuria, microalbuminuria and macroalbuminuria. Using a cut-off value of 14 ng/mg, nephrinuria was detected in 65% of women with normoalbuminuria, 95% with microalbuminuria and 100% with macroalbuminuria. Of the normoalbuminuric women who had an elevated urinary NCR (> 14 ng/mg), 78% were diagnosed with a hypertensive disorder and 63% were diagnosed with diabetes in pregnancy. In women with PE, urinary NCR and ACR were significantly higher when compared to women who did not develop PE. The AUC of the ROC for urinary NCR was 0.74 (95% CI: 0.650-0.824), with a sensitivity of 97% and a specificity of 36% to predict glomerular injury and a sensitivity of 93% and specificity of 42% to predict glomerular injury of PE. Conclusion: The study found that urinary NCR were elevated not only in women with micro- and macroalbuminuria but also in pregnant women with normoalbuminuria. Increased urinary NCR without increased urinary albumin may be associated with early glomerular injury. Urinary NCR may be a more sensitive marker than microalbuminuria to detect early glomerular injury in women with systemic disease and adverse pregnancy outcomes.
BACKGROUND:It has been well-established that the allostatic load (AL) index, a cumulative score of multi-system dysregulation in response to chronic stress, is significantly increased at the time of a psychiatric diagnosis. However, no studies have investigated if there is an association between the AL index in childhood and the later development of mental health symptoms in young adults. METHODS:Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population cohort from Bristol, United Kingdom, we investigated the AL index at age 9 years and the risks for mental health symptoms at age 24 years. We used multinomial logistic regression analysis to investigate the association between AL threshold (categorised into bottom third: AL index ≤ 7, middle third: AL index = 7.1-9.9, and top third: AL index ≥ 10) and mental health symptoms while adjusting for sex, the age of mother at delivery, and social class. We used a relative risk ratio (RRR) and 95 % confidence interval(CI) for each variable. We further investigated the association between adverse childhood experiences (ACEs) and mental health symptoms. RESULTS:We identified a significant association between sex and mental health symptoms, with more females (59 % vs 41 %) showing mental health symptoms than males. We found no direct association between the AL index at age 9 and the later development of mental health symptoms. However, an RRR analysis showed that individuals in the middle and the top third of the AL index had an RRR of 1.99 and 2.20, respectively, to develop mental health symptoms if they were females. We found that individuals who experienced ACE had a much higher risk of developing mental health symptoms as young adults, with the adjusted RRR of 5.39 (95 % CI: 3.00;9.67), 6.79 (95 % CI: 2.55; 18.1), and 2.10 (95 % CI: 0.37;11.8) for neglect, physical and sexual abuse, respectively, in individuals with mood disorder symptoms. The adjusted RRR for neglect and physical and sexual abuse in individuals with psychotic symptoms was 0.99 (95 % CI: 0.37; 2.59), 2.92 (95 % CI: 0.35; 24.4), and 10.5 (95 % CI: 0.99; 112), respectively. CONCLUSION:Although the AL index in childhood was not directly associated with the later development of psychotic and mood disorder symptoms in this cohort, females in the higher tertiles of the AL index measured at 9 years of age had an elevated risk of mental health symptoms as young adults. In line with previous work, a strong association was identified between childhood adversity and mental health symptoms in young adulthood. These results highlight the importance of considering the impact of early stress on biological embedding and the later emergence of mental health problems, especially in females.
The significance of intergenerational impacts on fetal and infant kidney development and function remains to be fully understood. This is particularly relevant for certain populations, for example the Indigenous Australians since their risk of developing chronic kidney disease (CKD) is twice that of non-Indigenous Australians. The aim of this study was to assess the impact of maternal health and kidney size and function on infant kidney development. This study was open to all pregnant women receiving antenatal care at Townsville University Hospital, Australia. It presents data from a larger, ongoing prospective, longitudinal cohort study which commenced August 2019, involving mother-infant dyads. This manuscript reports on term mother-infants’ dyads from singleton pregnancies. Ultrasound was used to measure renal parenchymal thickness, a surrogate for nephron number, of the mother and their newborn. Kidney function was assessed using serum cystatin C and creatinine. Analysis was conducted on 80 mother-infant dyads, 17 Indigenous and 63 non-Indigenous. Multivariate regression modeling showed maternal renal parenchymal thickness (ß = 0.31, p = 0.004), smoking (ß = − 0.70, p = 0.022) and maternal serum cystatin C (ß = − 0.34, p = 0.014) significantly predicted newborn renal parenchymal thickness. No significant differences were found between the maternal and newborn renal parenchymal thickness and function between Indigenous and non-Indigenous participants. Our study suggests that maternal kidney size and function has a significant intergenerational effect on kidney development of their infants. Newborn renal parenchymal thickness was positively associated with maternal renal parenchymal thickness and negatively associated with smoking and maternal serum cystatin C.
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.
The aim of the study was to investigate relationship between cord clamping status, total hemoglobin (THb) and total bilirubin (TBil) in term infants requiring phototherapy for neonatal jaundice. This retrospective study included term infants admitted at the study hospital for management of physiological neonatal jaundice between 2013 and 2019. Associations between THb, TBil, cord clamping status and Direct Coombs Test (DCT) status, as well as correlation between laboratory and blood gas analyzer (BGA) methods were investigated. 258 term infants were included. 147 infants had cord clamping status documented; 111 had unknown cord clamping status. Delayed cord clamping (DCC) was associated with significantly higher mean THb in DCT negative infants only. Negative DCT was associated with higher THb and TBil regardless of cord clamping status. Mean TBil concentration did not change with increasing THb or cord clamping status. The incidence of term infants admitted for phototherapy increased over the study period. There was strong positive correlation between BGA and laboratory assays. DCC was associated with a higher THb in DCT negative infants only. There was no correlation between THb and TBil. There was strong positive correlation of TBil between BGA and laboratory assays thus supporting BGA use in ambulatory care settings.
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. Graphical abstract
IntroductionThe 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.MethodsUsing 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.DiscussionThis 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.
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.
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 NaHCO 3 , 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 NaHCO 3 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 CaCl 2 ·2H 2 O, 1.1 mM MgSO 4 ·7H 2 O, 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.
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.