Weeks Of Age Research Articles

Correlation of Sonographic Gestational Age with Fetal Kidney Length in Normal Pregnancy

Precise evaluation of gestational age is essential for quality maternity care. Ultrasonography is the most readily available and reliable method to establish gestational age. This study aims to use the length of the fetal kidney as a reliable parameter to measure gestational age in late second and third trimesters. Objective: To determine the relationship between fetal kidney length and gestational age in weeks during the late 2nd and 3rd trimester of normal pregnancy. Methods: It was a prospective cross-sectional study conducted on 105 singleton normal pregnant females between 24th and 40th weeks of gestation who came to the obstetrics and gynecology department at a private sector hospital in Kharian, Pakistan. The duration of the study was four months. Bi-parietal diameter, femur length, and fetal kidney lengths were measured. Statistical analyses were applied using SPSS version 22.0. Results: A moderately significant positive correlation was identified between different gestational age measuring parameters and fetal kidney length. The correlation was significant at the level of 0.01. The correlational values of GA according to LMP with FKLL and FKLR were (r= .85**) and (r= .87**) respectively. GA with BPD indicates a moderately significant positive correlation with FKLL and FKLR (r= .94**) and (r=.94**). GA with FL also shows a moderately significant positive correlation with FKLL and FKLR (r= .83**) and (r= .83**), respectively. Conclusion: In conclusion, fetal kidney length in millimeters correlates well with gestational age in weeks and shows linear growth with gestational age throughout pregnancy. Gestational age estimated from fetal kidney length gives improved dating of fetal age

Apparent metabolizable energy, growth performance and carcass traits of Japanese quail fed select modern grain sorghum varieties.

This study was performed to determine the apparent metabolizable energy (AMEn) content of tannin-free red/bronze, white/tan and U.S. No. 2 varieties of grain sorghum for feeding Japanese quail and validate their nutrient profile by evaluating effects on performance and carcass traits with full-substitution of corn. Experiment 1 determined the AMEn content of red/bronze, white/tan, and U.S. No. 2 grain sorghum varieties fed to mixed-sex Japanese quail (Coturnix japonica) (n = 314) at 3 and 6-weeks of age. Analyses were based on a 2×4 factorial treatment design with age and grain types defining the treatments, and a randomized complete block experiment design with cage and trials defining the block. AMEn values were validated by evaluating the performance and carcass traits of Japanese quail (n = 644) from 1 to 40 days of age in Experiment 2 with birds were fed 1 of 4 complete diets. Statistical analyses were conducted on performance data and select individual carcass trait measurements. Determined AMEn values at 3-weeks of age were 3,524±122.03 (red/bronze), 3,252±122.03 (white/tan), and 3,039±123.44 (U.S. No. 2) kcal/kg. At 6-weeks of age, determined AMEn were 3,373±297.35 (red/bronze), 3,279±297.35 (white/tan), and 2,966±298.64 (U.S. No. 2) kcal/kg. Carcass traits showed live body weight (p = 0.0409) and hot carcass weight (p = 0.0234) were greatest in U.S. No. 2; however, carcass yield (p<0.0001) was lowest. No significant differences were observed among treatments for feed intake, feed conversion ratio, breast weight and breast yield (p>0.05). These studies demonstrated that tannin-free grain sorghum varieties may be a potential alternative to corn in quail diets while maintaining growth performance and carcass parameters.

Characterization of Endothelium-Dependent Relaxation in the Saphenous Artery and Its Caudal Branches in Young and Old Adult Sprague Dawley Rats.

Ageing is associated with reduced endothelium-derived nitric oxide (NO) production in the femoral artery of Sprague Dawley (SD) rats. In the current study, we examined endothelium-dependent relaxation (EDR) in the saphenous artery and its caudal branches. We used acetylcholine and the Proteinase-Activated receptor-2 (PAR2)-specific agonist (2fLIGRLO) with nitroarginine methylester (L-NAME) to assess EDR in two groups of male SD rats (age in weeks: young, 10–12; old, 27–29). Acetylcholine and 2fLIGRLO were potent NO-dependent relaxant agents in all arteries. For all arteries, EDR by acetylcholine decreased significantly in old compared to young SD rats. Interestingly, PAR2-induced EDR of proximal saphenous artery segments and caudal branches decreased significantly in old compared to young, but did not differ for the in-between middle and distal ends of the saphenous artery. L-NAME treatment increased subsequent contractions of proximal and middle segments of saphenous arteries by phenylephrine and U46619 in young, but not in old, SD rats. We conclude the SD saphenous artery and caudal branches exhibit regional characteristics that differ in response to specific EDR agonists, endothelial NO synthase inhibitor, and changes to endothelium function with increased age, which are, in part, attributed to decreased sensitivity of vascular smooth muscle to the gaseous transmitter NO.

Impaired mitophagy in Sanfilippo a mice causes hypertriglyceridemia and brown adipose tissue activation

Lysosomal storage diseases result in various developmental and physiological complications, including cachexia. To study the causes for the negative energy balance associated with cachexia, we assessed the impact of sulfamidase deficiency and heparan sulfate storage on energy homeostasis and metabolism in a mouse model of type IIIa mucopolysaccharidosis (MPS IIIa, Sanfilippo A syndrome). At 12-weeks of age, MPS IIIa mice exhibited fasting and postprandial hypertriglyceridemia compared with wildtype mice, with a reduction of white and brown adipose tissues. Partitioning of dietary [3H]triolein showed a marked increase in intestinal uptake and secretion, whereas hepatic production and clearance of triglyceride-rich lipoproteins did not differ from wildtype controls. Uptake of dietary triolein was also elevated in brown adipose tissue (BAT), and notable increases in beige adipose tissue occurred, resulting in hyperthermia, hyperphagia, hyperdipsia, and increased energy expenditure. Furthermore, fasted MPS IIIa mice remained hyperthermic when subjected to low temperature but became cachexic and profoundly hypothermic when treated with a lipolytic inhibitor. We demonstrated that the reliance on increased lipid fueling of BAT was driven by a reduced ability to generate energy from stored lipids within the depot. These alterations arose from impaired autophagosome–lysosome fusion, resulting in increased mitochondria content in beige and BAT. Finally, we show that increased mitochondria content in BAT and postprandial dyslipidemia was partially reversed upon 5-week treatment with recombinant sulfamidase. We hypothesize that increased BAT activity and persistent increases in energy demand in MPS IIIa mice contribute to the negative energy balance observed in patients with MPS IIIa.

Diet dilution and feeding frequency have only minor effects on the behaviour of broiler breeder pullets

During the rearing period, broiler breeders are feed restricted to prevent the negative impact of fast growth and high body weight on health and reproduction. Feed restriction causes frustration and stress, resulting in stereotypic pecking and hyperactivity. Nutritional strategies have the potential to reduce these welfare issues. Using a 2 × 2 factorial completely randomized block design, pullets were fed with two diet densities and two feeding frequencies during rearing. From 3–23 weeks of age (WOA), pullets received either a standard control diet (CON) or a 16% diluted diet (DIL) containing oat hulls. These diets were provided either once (FO) or twice (FT) a day. After 23 WOA, all pullets received the same standard layer diet once a day. Home pen behaviour was observed by scan sampling at 5, 10, 15, 20, 30 and 39 WOA over eight observation sessions. Furthermore, pullets were subjected to Novel Food Tests (12 and 17 WOA) and Novel Object Tests (5, 10, 15 and 20 WOA). Minor treatment effects were found for foraging and sitting behaviour that varied with age during rearing. Feeding frequency influenced the behavioural patterns of all home pen behaviours (P < 0.001; object pecking P = 0.034), while diet dilution only affected the expression of foraging behaviour during the day (P = 0.007). In all treatment groups, many pullets were observed standing and walking in anticipation of the first meal. After the first meal and before the second meal, more FT pullets were observed standing and walking, while during and after the second meal more FO pullets were observed sitting and performing comfort behaviour. Feeding twice a day resulted in lower daily peaks in drinking behaviour. In the laying period, when all birds received the same layer diet at the same frequency, those who were fed twice daily during rearing foraged more than those who were fed once (P = 0.028) and birds that received a diluted diet during rearing tended to drink more than birds that received the control diet (P = 0.083). Few treatment effects were found in the Novel Food and Novel Object Tests, indicating that diet dilution and/or feeding frequency, as applied here, did not affect fearful behaviour or the motivation to explore. In conclusion, this study showed that neither diet dilution, twice-daily feeding, or the combination of these, improved broiler breeder welfare during rearing and laying. Some changes in the pattern of home pen behaviour were found that indicated a response to the frequency of food provisioning.

Abstract 935: NEK1 phosphorylates YAP1 to promote prostate cancer tumorigenesis

Abstract Background: Prostate cancer (PCa) is the second leading cause of cancer death in men of western part of the world. The disease progression has been defined by substages (adenocarcinoma to castration resistant PCa to neuroendocrine PCa) both from mouse models and patients from clinical studies. The mechanism of the disease advancement and hence treatment modalities is still under investigation. Hippo pathway, the evolutionarily conserved developmental pathway, known to regulate organ size, proliferation, apoptosis, migration, stemness etc., is also implicated in PCa tumorigenesis. Transcriptional co-activator YAP1 which acts downstream of the canonical hippo kinases is known to interact with plethora of proteins. But how non-canonical hippo kinases can regulate YAP1 in this disease is yet to be unraveled. We find that NIMA-related kinase isoform 1, Nek1, interacts with YAP1 and phosphorylates Tyr-407 of YAP1. The significance of this post-translational modification is the focus of the study. We find that Nek1 phosphorylates YAP1 to stabilize YAP1 and promote tumorigenesis. Material and Methods: Human YAP1 cDNA encoding plasmid mutated at Tyr 407 to Phenylalanine using site-directed mutagenesis. YAP1-Y407F and WT expressed in HEK293A cells. For genetic analysis in mouse model, female TRAMP mice were bred with Nek1 -/+ male mouse (Jackson laboratory). Genotypic analysis confirmed Nek1-/+ TRAMP and Nek1+/+TRAMP which were used for this study. After 16weeks of age the male mice were castrated and sacrificed at 20weeks of age. Prostate tissues collected and histological sections done (paraffin embedded). Immunohistochemical (IHC) analysis was done using vector labs IHC kits, data analyzed and scored by our pathologist. Results: Immunoblots from YAP1-Y407F and WT cells treated with Cycloheximide (50ug/ml) at different time points (0.5-6hrs) show that YAP1-Y407F is less stable than WT with t1/2 of 0.5hrs whereas WT is stable till 2hrs. Very importantly, while intact TRAMP/Nek1+/- mice do develop PCa normally with much enlargement of the prostate at 18-20 weeks, if these mice are castrated, the tumors fail to grow and the prostate retains normal size and general morphology. Our IHC data confirms that firstly, castrated Nek1+/+TRAMP shows clearly cancerous acini whereas the Nek-/+ TRAMP shows mostly stromal fibrosis and hyperplasia (as shown in H&amp;E and IHC). Secondly, when stained for activated Nek1 marker, pNek1 (T141), we find that Nek1 stain intensity is low in Nek1-/+ tissues compared to Nek1+/+. Most importantly, YAP1 level is lower in the same parallel tissue sections of Nek1-/+. From the above analysis, we conclude that Nek1 activity regulates stability of YAP1, and infer that YAP1 function is critical for the timely progression to adenocarcinoma following androgen deprivation therapy. Acknowledgements: Funding Resources: Department of Defense (DoD-PCRP grant W81XWH-17-1-0417) ; FWCC Bridge Award. Citation Format: Ishita Ghosh, Zobair Alam, Md. Imtiaz Khalil, Judy King, Arrigo DeBenedetti. NEK1 phosphorylates YAP1 to promote prostate cancer tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 935.

Associations between ambient temperature and risk of preterm birth in Sweden: A comparison of analytical approaches

BackgroundEvidence indicates that high temperatures are a risk factor for preterm birth. Increasing heat exposures due to climate change are therefore a concern for pregnant women. However, the large heterogeneity of study designs and statistical methods across previous studies complicate interpretation and comparisons. We investigated associations of short-term exposure to high ambient temperature with preterm birth in Sweden, applying three complementary analytical approaches. MethodsWe included 560,615 singleton live births between 2014 and 2019, identified in the Swedish Pregnancy Register. We estimated weekly mean temperatures at 1-km2 spatial resolution using a spatiotemporal machine learning methodology, and assigned them at the residential addresses of the study participants. The main outcomes of the study were gestational age in weeks and subcategories of preterm birth (<37 weeks): extremely preterm birth (<28 weeks), very preterm birth (from week 28 to <32), and moderately preterm birth (from week 32 to<37). Case-crossover, quantile regression and time-to-event analyses were applied to estimate the effects of short-term exposure to increased ambient temperature during the week before birth on preterm births. Furthermore, distributed lag nonlinear models (DLNM) were applied to identify susceptibility windows of exposures throughout pregnancy in relation to preterm birth. ResultsA total of 1924 births were extremely preterm (0.4%), 2636 very preterm (0.5%), and 23,664 moderately preterm (4.2%). Consistent across all three analytical approaches (case-crossover, quantile regression and time-to-event analyses), higher ambient temperature (95th vs 50th percentile) demonstrated increased risk of extremely preterm birth, but associations did not reach statistical significance. In DLNM models, we observed no evidence to suggest an increased effect of high temperature on preterm birth risk. Even so, a suggested trend was observed in both the quantile regression and time-to-event analyses of a higher risk of extremely preterm birth with higher temperature during the last week before birth. ConclusionsIn Sweden, with high quality data on exposure and outcome, a temperate climate and good quality ante-natal health care, we did not find an association between high ambient temperatures and preterm births. Results were consistent across three complementary analytical approaches.

LGG-54. Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia

To elucidate the mechanisms underlying the reduced incidence of brain tumors in children with Neurofibromatosis type 1 (NF1) and asthma, we leverage optic pathway glioma (Nf1-OPG) mice, human and mouse RNAseq data, and two different experimental asthma models. Following ovalbumin or house dust mite asthma induction at 4-6 weeks of age (WOA), Nf1-OPG mouse optic nerve volumes and proliferation are decreased at 12 and 24 WOA, indicating no tumor development. This inhibition is accompanied by reduced expression of the microglia-produced optic glioma mitogen, Ccl5. Human and murine T cell transcriptome analyses reveal that inhibition of microglia Ccl5 production results from increased T cell expression of decorin, which blocks Ccl4-mediated microglia Ccl5 expression through reduced microglia NFκB signaling. Decorin or NFkB inhibitor treatment of Nf1-OPG mice at 4-6 WOA inhibits tumor formation at 12 WOA, thus establishing a potential mechanistic etiology for the attenuated glioma incidence observed in children with asthma.

Mice blocking Ser347 phosphorylation of pregnane x receptor develop hepatic fasting-induced steatosis and hypertriglyceridemia

Nuclear receptor Pregnane X Receptor (PXR; NR1I2) has transcriptional regulation functions for energy homeostasis in the liver. Mouse PXR has a conserved phosphorylation motif at serine 347 (serine 350 in humans) within the ligand-binding domain. PXR phosphorylated at this motif is expressed in mouse livers in response to fasting. Mice with a PXR∗Ser347Ala knockin mutation (PXR KI) were generated to block phosphorylation, and utilized to investigate the role of Ser347 phosphorylation in vivo. PXR KI mice had decreased body weight at 8-weeks of age and had much greater weight loss after fasting compared with PXR WT mice. The cDNA microarray analysis of hepatic mRNAs showed that cell death or apoptotic signaling was induced in fasting PXR KI mice. Moreover, increasing hepatic lipids, triglycerides and the development of hypertriglyceridemia were observed in fasting PXR KI mice. These findings are indicative that blocking phosphorylation prevents mice from maintaining hepatic energy homeostasis. Thus, phosphorylated PXR may be an essential factor to prevent the liver from developing damage caused by fasting.

Determinants of rapid infant weight gain: A pooled analysis of seven cohorts.

SummaryObjectiveRapid weight gain (RWG) in infancy is strongly associated with subsequent obesity risk, but little is known about the factors driving RWG. This study explored the child and maternal factors associated with infant RWG.MethodsData from seven Australian and New Zealand cohorts were used (n = 4542). Infant RWG was defined as a change in weight z‐score ≥0.67 from birth to age 1 year. Univariable and multivariable logistic regression assessed the association between child and maternal factors and infant RWG in each cohort. Meta‐analysis was conducted to obtain pooled effect sizes.ResultsMultivariable analyses revealed boys were more likely to experience RWG (OR 1.42 95% CI 1.22, 1.66) than girls. Higher birth weight in kg (OR 0.09, 95% CI 0.04, 0.20) and gestational age in weeks (OR 0.69, 95% CI 0.48, 0.98) were associated with lower RWG risk. Children who were breastfed for ≥6 months showed lower RWG risk (OR 0.45, 95% CI 0.38, 0.53). Children of native‐born versus overseas‐born women appeared to have higher RWG risk (OR 1.37, 95% CI 0.99, 1.90). Maternal smoking during pregnancy increased RWG risk (OR 1.60, 95% CI 1.28, 2.01), whereas children who started solids ≥6 months (OR 0.77, 95% CI 0.63, 0.93) and children with siblings (OR 0.68, 95% CI 0.57, 0.81) showed lower RWG risk in univariable analysis, but these associations were attenuated in multivariable analysis. No association was found for maternal age, education, marital status and pre‐pregnancy BMI.ConclusionMaternal country of birth, smoking status, child sex, birth weight, gestational age, infant feeding and parity were potential determinants of infant RWG.

Effect of adrenalectomy and insulin resistance on non‐shivering thermogenesis in the corpulent rat

Glucocorticoid hormones have been reported to impede optimal insulin sensitivity and glucose uptake in peripheral tissues via interactions with GLUT transporters, leading to insulin resistance and impaired glucose uptake via GLUT transporters. The LA/Ntul//‐cp rat expresses obesity in 25% of the offspring by 5 to 6 weeks of age but remains non diabetic throughout much if not all of its lifespan when normally reared. Groups of congenic lean and obese LA/Ntul//‐cp rats were fed low glycemic Purina Chow diets from 6 to 9 weeks of age or overfed with a high energy cafeteria diet (Café) from 9 until 12 weeks of age. Subgroups of obese animals were adrenalectomized (ADX) at 6 weeks of age (WoA) and subjected to the same dietary regimen to determine if the Café overfeeding could enhance the normal thermic response to norepinephrine (NE) in the obese phenotype and to determine if ADX would result in a restoration of glycemic status and NE‐induced thermogenesis in the obese phenotype. Measures of Oral Glucose Tolerance (OGT), Area under the glucose curve (AUC), and NE‐stimulated VO2 were determined (NE, 200 µg, s.c.) at 6, 9 and 12 WoA in all treatment groups and Insulin:Glucose ratios (I:G) at 12 WoA. Obese animal demonstrated hyperphagia at all ages studied, and Obese ADX hyperphagia from 9 to 12 WoA. OGT and AUC indicated modest glucose intolerance in the obese phenotype, and which was restored following ADX at 6 and 9 WoA. NE resulted in a progressive increase in VO2 in lean rats at each age studied, but NE‐stimulated VO2 was lower in the obese phenotype and decreased further after the Café feeding regimen. ADX was associated with a restoration of OGT, I:G and NE stimulated VO2 equivalent to that observed in lean animals at 12 weeks of age. These results are consistent with adrenocorticoid‐mediated insulin resistance likely due to a receptor level defect in insulin sensitivity as a contributory factor in the impairment in OGT and NST in the obese phenotype of this strain.

Lowering of Sympathetic Burst Frequency in Post‐Pubertal Female but not Male Rats

INTROCardiovascular disease (CVD) leads to an overall reduction in the quality of life and is the leading cause of mortality in the United States. The risk of CVD increases with age; however, women of reproductive age have a lower CVD prevalence. CVD is associated with elevations in sympathetic nerve activity, which has been analyzed in humans by quantifying sympathetic burst frequency. Whether sympathetic burst frequencies are different between pre‐ and post‐pubertal males and females is unknown.PURPOSEThe purpose of this study was to analyze sympathetic burst frequencies for potential differences between male and female rats.HYPOTHESISWe hypothesized that resting sympathetic burst frequency would be lower in post‐pubertal females compared to age‐matched males. We also predicted lower burst frequency in post‐ versus pre‐pubescent females.METHODSWe analyzed splanchnic nerve (SSNA) recordings from Inactin‐anesthetized male and female Sprague‐Dawley rats at 4‐weeks (pre‐pubertal) and 8‐ and 16‐weeks (post‐pubertal) of age. Sympathetic bursts were obtained by rectifying and integrating raw SSNA. Burst frequency was calculated using the Peak Parameters extension in LabChart software.RESULTSBurst frequency was higher in 4‐week (n=8) and 8‐week (n=9) old female rats compared to 16‐week old (n=6) female rats (5.6+1.2; 4.8+0.4 and 2.4+0.3 Hz, p&lt;.001 and p=0.02, respectively). At 16 weeks of age, female rats also had a significantly lower burst frequency when compared to male rats (n=4) (2.4+0.3 vs, 4.8+0.4 Hz, respectively, p=0.01). Finally, there was no significant difference found in burst frequencies between male rats at any age (p&gt;0.05 for all), suggesting sex‐dependent differences in the development of sympathoexcitation.CONCLUSIONPreliminary results suggest that following the onset of puberty in female rats, sympathetic burst frequency decreases over time, changes not seen in age‐matched male rats. Given CVD is significantly lower in premenopausal women, lower sympathetic nerve activity as a result of puberty may provide a mechanistic basis by which decreased sympathetic burst frequency protects against CVD. Future experiments may be conducted to explore other burst characteristics (e.g. burst amplitude and width), and the role of specific female sex hormones, to further understand sex‐dependent development of CVD.

Abstract 292: LRP1 Prevents Aortic And SMA Aneurysms By Modulating Excessive Ang-II Signaling

Objectives: LRP1 (low-density lipoprotein receptor-related protein 1) is known to contribute to vascular homeostasis and plays a protective role against the development of aneurysms. LRP1 has specifically been associated with abdominal aortic aneurysms in GWAS studies. We and others have also previously reported that mice with a conditional smooth muscle cell (SMC) knock-out of LRP1 (smLRP1-/-) exhibit vascular wall dysfunction and aortic dilation. In this study, we sought to investigate the molecular mechanisms by which LRP1 regulates vessel wall integrity in hopes of identifying potential therapeutic targets against aneurysm progression. Approach and Results: Analysis of proteomic data of the descending thoracic aorta, abdominal aorta, and superior mesenteric artery (SMA) of smLRP1-/- mice confirmed excess activation of the angiotensin signaling pathway. To verify these observations, we designed experiments to determine if losartan, an angiotensin-II receptor blocker, could prevent aneurysm progression in smLRP1-/- mice. Following treatment, we analyzed the aortic vasculature from LRP1+/+ and smLRP1-/- adult mice (16-weeks of age) with or without treatment. Without losartan, smLRP1-/- mice developed spontaneous aortic and SMA aneurysms as demonstrated by increased vessel dilation, vessel medial thickening and significant fragmentation of the elastic lamina. We found that when treated with losartan, smLRP1-/- mice had a complete restoration of medial layer thickness and a partial decrease of elastin fragmentation compared to untreated smLRP1-/- mice. Furthermore, losartan completely blocked SMA aneurysm formation in smLRP1-/- mice. Conclusions: Our findings suggest a critical role for LRP1 in maintaining vascular homeostasis and preventing aneurysm formation through its regulation of the angiotensin signaling pathway. Further studies will need to investigate the connection between LRP1 and the angiotensin signaling pathway in aneurysm formation to further understand the complex pathophysiology and potentially develop effective therapeutic targets for this disease.

Developing A Reference Charts for Foetal Biometry in Indian Population to Predict Growth &amp; Development of Foetus

ObjectivesThe objective of the study was to develop reference charts for foetal abdominal circumference and femur length in normal singleton pregnancies. The modality used in the study was by means of ultrasonography which is easily available and safe during the pregnancy.MethodIn this study, we conducted ultrasonography examination in 300 singleton pregnant women coming for routine checkups. Out of various foetal biometric parameters abdominal circumference (AC) and femur length (FL) were measured and reference charts (10th, 50th, 90th and 95th percentiles) for each parameter corresponding to its gestational age were developed.ResultsAge distribution of pregnant women was uniform (p=0.87). Both parameters i.e. AC and FL were found to be in linear correlation with the corresponding gestational age in weeks. Therefore, their use in determining development and age of the foetus is reliable. We compared our reference charts with other studies conducted in European and Chinese population. From which, it is obvious that the data found in Indian population is different from studies conducted in other ethnic population.ConclusionReference charts derived in this study can be used to determine growth and development of foetus depending upon Indian standards. Because ethnicity, race, nutritional and environmental factors are known to impact the foetal development. Most of the health care set ups are using data from the studies conducted in western population. Which may cause misrepresentation of data in diagnosis. Thus can lead to unnecessary medical intervention which may cause burden in limited resources in developing nations like India. Therefore, we conclude that each population should have their own reference charts for foetal biometry.

Diet-induced hypertension in rats is associated with increased renal vasoconstrictor response to angiotensin II after imitated endothelial dysfunction.

The mechanisms behind development of diet-induced hypertension remain unclear. The kidneys play a paramount role in blood volume and blood pressure regulation. Increases in renal vascular resistance lead to increased mean arterial blood pressure (MAP) due to reduced glomerular filtration rate and Na+ excretion. Renal vascular resistance may be increased by several factors, e.g. sympathetic output, increased activity in the renin-angiotensin system or endothelial dysfunction. We examined if a 14-week diet rich in fat, fructose or both led to increased renal vascular resistance and blood pressure. Sixty male Sprague-Dawley rats received normal chow (Control), high-fat chow (High Fat), high-fructose in drinking water (High Fructose), or a combination of high-fat and high-fructose diet (High Fat + Fruc) for 14weeks from age 4-weeks. Measurements included body weight (BW), telemetry blood pressures, renal blood flow in anesthetized rats, plasma concentrations of atrial natriuretic peptide and glucose, as well as vessel myography in renal segmental arteries. Body weight increased in both groups receiving high fat, whereas MAP increased only in the High Fat + Fruc group. Renal blood flow did not differ between groups showing that renal vascular resistance was not increased by the diets. After inhibiting nitric oxide and prostacyclin production, renal blood flow reductions to Angiotensin II infusions were exaggerated in the groups receiving high fructose. MAP correlated positively with heart rate in all rats tested. Our data suggest that diet-induced hypertension is not caused by an increase in renal vascular resistance. The pathophysiological mechanisms may include altered signaling in the renin-angiotensin system and increases in central sympathetic output in combination with reduced baroreceptor sensitivity leading to increased renal vasoconstrictor responses.

Transiently increased serotonin has modest or no effects on bone mass accrual in growing female C57BL6/J or growing male and female Lrp5A214V mice.

Serotonin (5HT) is a chemical messenger with biologic activities affecting multiple organs. Within the skeletal system, studies in mice and humans suggest blood 5HT levels affect bone, with elevations impairing and reductions enhancing bone accrual. Other studies, however, have not supported this hypothesis. Recently, administering 5HT to a Piezo1 mutant mouse strain with hyposerotonemia, intestinal dysmotility, and a doubling of femoral trabecular bone mass at 2months of age, was reported to return the animals' intestinal motility and bone mass to normal. However, whether the 5HT directly affected bone metabolism or indirectly affected metabolism by improving intestinal function was not determined. Therefore, we administered 5HT to mice with normal intestinal function. We randomized female C57BL6/J mice and male and female mice that have increased bone mass due to a missense mutation in the WNT co-receptor LRP5 (Lrp5A214V) to receive 5HT or vehicle via daily IP injection from 4weeks to 8weeks of age. We did not observe consistent significant changes for distal femur trabecular, midshaft femur cortical, or vertebral body trabecular bone mass between 5HT treated and vehicle treated mice of either genotype. These data are compatible with other studies that have not observed a correlation between blood 5HT level and bone mass.

Thick ascending limb specific inactivation of Myh9and Myh10 results in progressive kidney disease with sexually dimorphic sodium transport regulation

Mutations in MYH9 gene that encodes for actin associated molecular motor nonmuscle myosin II (NM2) result in kidney disease in some patients. Based on our previous work that demonstrated a novel role for NM2 motors, we hypothesized that NM2 genes might play a critical role in renal epithelial transport. To test our hypothesis, we generated pan renal tubular conditional knockout (cKO) of Myh9&amp;10 in adult mice that resulted in progressive kidney disease of TAL origin with aberrant transport of TAL cargoes UMOD and NKCC2 (Otterpohl et al; 2020). To confirm the cell‐autonomous role for NM2 proteins in adult TAL epithelium, we generated a TAL‐specific cKO mouse model of Myh9&amp;10using a TAL specific cre transgenic mice, UMOD‐&gt;CreERT2. Cre transgene was induced at 5 weeks of age with tamoxifen injections, age matched control and cKO littermates were part of every cohort. The mice underwent metabolic, histologic, immunohistochemical, and biochemical analysis at varying time points until moribund. The TAL‐specific Myh9&amp;10 cKO mice develop progressive kidney disease indicated by increase in BUN and serum creatinine as well as increasing levels of the tubular injury marker, NGAL. Our results show that Myh9&amp;10 TAL‐ cKO females had significant loss of weight at 12 weeks, the female cKO animals became moribund between 13 – 14 weeks, while the male cohorts survive up to 25 weeks. Histology confirmed the tubulointerstitial disease in Myh9&amp;10 TAL‐cKO with dilated tubules and cellular infiltration. Urine pH declined starting at 9‐weeks of age in females and 12‐week in males. Interestingly, female cKO mice have hypernatremia at 12‐weeks of age compared to male mice which maintain normal sodium levels. Since the pan renal tubular Myh9&amp;10 cKO exhibited loss of NKCC2 leading to salt wasting, this result was unexpected. We analyzed NKCC2 protein levels in kidney lysates, loss of NKCC2 was evident in both female and male Myh9&amp;10 TAL‐cKO. We also observe significant decline in serum potassium levels in 7.5‐week females. We speculated that the hypernatremia in TAL‐Myh9&amp;10 cKO females is due to tubular adaptation in the distal nephron and the collecting duct. Characterization of sodium cotransporters and channels in distal nephron and collecting duct segment revealed an increase in NCC/pNCC levels in males and a decrease in females. Immunostaining experiments showed increase in ENaC gamma expression in the cortical collecting ducts of the females. This could potentially explain the hypernatremia and early morbidity observed in Myh9&amp;10 TAL‐cKO females. We speculate that females upregulate ENaC gamma to compensate for loss of NKCC2, instead males upregulate NCC/pNCC that prevents their early lethality. These experiments confirm the critical role for Myh9&amp;10 proteins in TAL tubule and identify a novel, sex specific tubular adaptation mechanisms. NM2 motor regulating the unique, TAL‐specific sodium cotransporter is intriguing and warrants further analysis. Our model also provides a good resource for understanding the sex‐specific differences of sodium handling and potentially clarify mechanisms underlying Type I Bartter Syndrome.

Exposure to Fluoride From in Utero to Puberty Alters Gonadal Structure and Steroid Hormone Expression in Offspring Rats.

The reproductive toxicity of fluoride has been proven by a large number of studies. While the underlying mechanism of reproductive toxicity during pregnancy is still unclear. Hence, in this study, we investigated the effects of fluoride exposure on ovarian and testicular steroid hormone synthesis in young and adult rat offspring. We established a model of fluoride-exposed rat pups from in utero to puberty to explore the mechanisms of fluoride impacts on reproductive toxicity in the offspring. The results showed that NaF exposure did not affect the 3weeks of age offspring. Whereas the body weight in both sexes significantly decreased, and the ovarian and testicular tissue structures were damaged at 11weeks of age. In females, the total number of secondary follicles and mature follicles were significantly reduced after NaF exposure. Moreover, estradiol (E2) and follicle-stimulating hormone (FSH) levels in the females were significantly reduced in the 100mg/L NaF exposure group. In males, the sperm viability and testosterone (T) were significantly decreased in the NaF exposure groups. Additionally, during steroidogenesis in ovaries and testes, fluoride remarkably decreased the expression levels of genes and proteins, including acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), cytochrome P450 17a-hydroxylase (CYP17A1), and cholesterol side-chain cleavage enzyme (CYP11A1), while the mRNA levels of 17β-hydroxysteroid dehydrogenase (17β-HSD) decreased only in the testes. These results indicated that fluoride exposure disrupted the steroid hormone balance by changing several important steroidogenic-related genes associated with the development of the gonads, and damage the normal structure of the gonads in rat offspring.

Nasopharyngeal Dysbiosis Precedes the Development of Lower Respiratory Tract Infections in Young Infants, a Longitudinal Infant Cohort Study

Background: Infants suffering from lower respiratory tract infections (LRTIs) have distinct nasopharyngeal (NP) microbiome profiles that correlate with severity of disease. Whether these profiles precede the infection or a consequence of it, is unknown. In order to answer this question, longitudinal studies are needed. Methods: We conducted an analysis of a longitudinal prospective cohort study of 1,981 Zambian mother-infant pairs who underwent NP sampling from 1-week through 14-weeks of age at 2-3-week intervals. Ten of the infants in the cohort who developed LRTI were matched 1:3 with healthy comparators. We completed 16S rRNA gene sequencing on the samples each of these infants contributed, as well as from baseline samples of the infants’ mothers, and characterized the normal maturation of the healthy infant NP microbiome, compared to infants who developed LRTI. Results: The infant NP microbiome maturation was characterized by transitioning from Staphylococcus dominant to respiratory-genera dominant profiles during the first three months of life, similar to what is described in the literature. Interestingly, infants who developed LRTI had NP dysbiosis before infection, in most cases as early as the first week of life. Dysbiosis was characterized by the presence of Novosphingobium, Delftia, high relative abundance of Anaerobacillus, Bacillus, and low relative abundance of Dolosigranulum, compared to the healthy controls. Mothers of infants with LRTI also had low relative abundance of Dolosigranulum in their baseline samples compared to mothers of infants that did not develop an LRTI. Conclusions: Our results suggest that NP microbiome dysbiosis precedes LRTI in young infants and may be present in their mothers as well. Early dysbiosis may play a role in the causal pathway leading to LRTI or could be a marker of other pathogenic forces that directly lead to LRTI.

Grandmaternal exercise improves metabolic health of second-generation offspring

ObjectiveA major factor in the growing world-wide epidemic of obesity and type 2 diabetes is the increased risk of transmission of metabolic disease from obese mothers to both first (F1) and second (F2) generation offspring. Fortunately, recent pre-clinical studies demonstrate that exercise before and during pregnancy improves F1 metabolic health, providing a potential means to disrupt this cycle of disease. Whether the beneficial effects of maternal exercise can also be transmitted to the F2 generation has not been investigated. MethodsC57BL/6 female mice were fed a chow or high-fat diet (HFD) and housed in individual cages with or without running wheels for 2 wks before breeding and during gestation. Male F1 offspring were sedentary and chow-fed, and at 8-weeks of age were bred with age-matched females from untreated parents. This resulted in 4 F2 groups based on grandmaternal treatment: chow sedentary; chow trained; HFD sedentary; HFD trained. F2 were sedentary and chow-fed and studied up to 52-weeks of age. ResultsWe find that grandmaternal exercise improves glucose tolerance and decreases fat mass in adult F2 males and females, in the absence of any treatment intervention of the F1 after birth. Grandmaternal exercise also improves F2 liver metabolic function, including favorable effects on gene and miRNA expression, triglyceride concentrations and hepatocyte glucose production. ConclusionGrandmaternal exercise has beneficial effects on the metabolic health of grandoffspring, demonstrating an important means by which exercise during pregnancy could help reduce the worldwide incidence of obesity and type 2 diabetes.