Weeks Of Age Research Articles

Effects of neonatal rearing by different types of foster mother on the distribution of corticotropin-releasing factor neurons in the central amygdaloid nucleus in rats.

The mother-child relationship of newborns plays an essential role in the development of the central nervous system, and an inadequate relationship, such as mother-child separation, can cause deficits of mental function in adulthood. However, insufficient research has examined the effects of foster mothers. We assigned some neonatal rats to one of two foster mothers: one that was lactating and feeding her first litter (FL group) and one that had one previous experience of childbirth and feeding but no current litter (FE group). Other pups were raised by their own mother (OM group) or subjected to maternal separation (MS group). Pups were placed with the foster mother (FL and FE groups) or separated from their mother (MS group) for 3h/day on postnatal days 1-20. At age 6weeks, each group was divided into two subgroups, one with 30min of acute restraint stress loading (FL-R, FE-R, OM-R, and MS-R) and one without it (FL, FE, OM, and MS). Then, we compared the density of corticotropin-releasing factor-immunoreactive (CRF-ir) neurons in the central amygdaloid nucleus (CeA). The density of CRF-ir neurons in the CeA was significantly lower in the FL-R and MS-R subgroups than in the FL and MS subgroups, respectively. The results suggest that differences in care received during the neonatal period affect maturation of CRF neurons in the CeA and may have negative effects on the synthesis and release of CRF.

PSXIII-5 Effects of Stocking Density on the Welfare and Immune Responses of Laying Hens Housed in Small Furnished Cages

Abstract To investigate the effects of stocking density on the welfare and immune responses of laying hens housed in furnished cages, 192 Hy-Line Brown hens were housed in small furnished cages and randomly divided into three groups on their 18 weeks old for low-density group (833 cm2 per hen, LD), medium-density group (625 cm2 per hen, MD), and high-density group (500 cm2 per hen, HD). There are eight cages in each stocking density. The welfare of laying hens was assessed at 22, 42 and 72 weeks of age (WOA) for feather quality, foot cleanness, footpad dermatitis, hyperkeratosis and keel bone damage. After the last welfare assessment, venous blood from the wing of the hen was extracted for testing immune indicators of Immunoglobulin Y (Ig Y), Interferon gamma (IFN-γ), Transforming growth factor beta (TGF-β), Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-12 (IL-12) by enzyme-linked immunosorbent assay (ELISA). Results showed that feather quality of laying hens from HD group was worse than hens from LD and MD groups at 42 and 62 WOA (P < 0.05). The foot cleanness score of hens from HD group was worse than other two group hens at 62 WOA (P < 0.05), respectively. There was no significant difference between three groups on other welfare indicators (P > 0.05), but the welfare quality of laying hens got worse with the aging of laying hens. Laying hens from LD group had greater concentrations of serum IFN-γ, IL-2, IL-6 compared with hens from MD and HD groups (P < 0.05). There was no significant difference for other immune responses (P > 0.05). These findings suggest that keeping a high stocking density of laying hens could cause feather damage, impact the welfare quality and reduce the immune responses of laying hens housed in small furnished cages.

Age and sex related changes in fattening performance, dermatitis, intestinal histomorphology, and serum IgG level of slow- and fast-growing broilers under the intensive system.

Due to consumers' concerns about broiler welfare, slow-growing broilers (SGB) have also been used in production. Fast-growing broilers (FGB) reach slaughter weight earlier the slow growing. This study was aimed to determine the sex-related changes in fattening performance, dermatitis, intestinal histomorphology, and serum IgG level of SGB and FGB under the intensive system during the 10weeks. A total of 336 one-day-old broilers were distributed into four equal groups (FGB-female, FGB-male, SGB-female, and SGB-male) consisting of a 2 × 2 factorial design. The main factors were genotype (FGB and SGB) and sex (female and male). Each treatment had 6 duplicates consisting of 14 broilers. They were placed on the litter pens. The experiment lasted 10weeks. The body weight, body weight gain, feed consumption, and feed-to-gain ratio were determined weekly during the experiment. One broiler close to the average body weight from each pen (6 broilers in the group) has been slaughtered each week and intestinal histomorphology was determined. Additionally, IgG levels in the blood and dermatitis were determined. While the period in which the body weight gain was the highest in the FGB was up to 6week of age, this period lasted until the 7week of age in the SGB (P < 0.001). It has been determined that FGB have the best feed efficiency ability during both 6weeks of fattening period and 10weeks of fattening period (P < 0.001). The difference between the sex in terms of the feed efficiency appeared after the age of 4weeks and this difference continued until the age of 9weeks (P < 0.01). It was determined that villus height, crypt depth, and the ratio of villus height to crypt depth in the jejunum region were higher in FGB from the age of 1week than in SGB (P < 0.05). It was observed that the incidence of dermatitis increased in the FGB (P < 0.001). It has been determined that the genotype (P < 0.01) and period (P < 0.001) were effective according to the IgG level. These results indicate that 7 and 8weeks can be considered important periods in terms of economic efficiency in SGB and FGB reared for 10weeks under the same management systems and it was observed that both genotypes would be more susceptible to diseases at the age of 6weeks.

Prospective cross-sectional study to assess the correlation of placental thickness with gestational age and fetal weight among pregnant women

Aim: The goal of the current study was to determine the average placenta thickness and foetus weight for each group of gestational age, as well as the relationship between placenta thickness and foetus weight for pregnant Indian women of various gestational ages. Methods: 202 pregnant women were included as study subjects in the current study utilising a convenient sample technique. The antenatal women underwent an ultrasound examination to measure placental thickness, gestational age, and fetus weight. The correlation between the gestational age in weeks, placental thickness in cm, and foetal weight in gram was determined using the Pearson's Correlation (r value). Statistical significance was defined as a P value of 0.05 or lower. Results: The mean placental thickness increased significantly from first follow up (1.61±0.26 cms) to second follow up (2.62±0.07 cms) and third follow up visit (3.35±0.26 cms). The mean placental thickness increased significantly from first follow up (1.61±0.26 cms) to second follow up (2.62±0.07 cms) and third follow up visit (3.350±0.26 cms). The estimated gestational age (11–20 weeks) had a 79.9% variability (R2) based on placental thickness (mm).

Leucine-rich repeat kinase 2 is protective during acute kidney injury through its activation of autophagy in podocytes.

Leucine-rich repeat kinase 2 (LRRK2) is a known regulator of autophagy in a range of cell types. Here, we investigated the role of LRRK2-associated autophagy during acute kidney injury (AKI) and its underlying mechanism(s) of action. Male mice aged 8-weeks were treated with the LRRK2 inhibitor MLi-2 and exposed to lipopolysaccharide (LPS) through intraperitoneal injection or ischemia-reperfusion (IR) surgery. Mice were sacrificed 12 or 24 h post-LPS injection or IR operation and blood was collected for serum creatinine measurements. Kidney cortical tissues were collected for western blot analysis of podocyte-specific markers and autophagy-associated proteins. Renal histopathology was observed through hematoxylin-eosin staining. For cell-based assays, immortalized mouse podocytes were silenced for LRRK2 through siRNA transfection and exposed to LPS or cobalt chloride. Changes in cell viability were investigated using cell counting kit-8, flow cytometry and MTT assays. Expression of podocyte-specific markers and autophagy-associated proteins were analyzed by western blotting. We observed an increase in LRRK2 expression at 12 h post-LPS injection and IR surgery that was accompanied by enhanced autophagy. At 24 h post-treatment, both LRRK2 expression and autophagy declined. Kidney injury was most pronounced in mice treated with MLi-2. Podocytes silenced for LRRK2 showed a loss of cell viability, decreased levels of podocyte-specific protein expression and a suppression of autophagy. Together, these data reveal the protective effects of LRRK2 during AKI through enhanced podocyte autophagy and cell viability.

Bone matrix quality in a developing high-fat diet mouse model is altered by RAGE deletion.

Overweightness and obesity in adolescents are epidemics linked to chronic low-grade inflammation and elevated fracture risk. The increased fracture risk observed in overweight/obese adolescence contrasts the traditional concept that high body mass is protective against fracture, and thus highlights the need to determine why weight gain becomes detrimental to fracture during growth and maturity. The Receptor for Advanced Glycation End products (RAGE) is a central inflammatory regulator that can influence bone metabolism. It remains unknown how RAGE removal impacts skeletal fragility in overweightness/obesity, and whether increased fracture risk in adolescents could result from low-grade inflammation deteriorating bone quality. We characterized the multiscale structural, mechanical, and chemical properties of tibiae extracted from adolescent C57BL/6J (WT) and RAGE null (KO) mice fed either low-fat (LF) or high-fat (HF) diet for 12weeks starting at 6weeks of age using micro-computed tomography, strength, Raman spectroscopy, and nanoindentation. Overweight/obese WT HF mice possessed degraded mineral-crystal quality and increased matrix glycoxidation in the form of pentosidine and carboxymethyl-lysine, with HF diet in females only showing reduced cortical surface expansion and TMD independently of RAGE ablation. Furthermore, in contrast to males, HF diet in females led to more material damage and plastic deformation. RAGE KO mitigated glycoxidative matrix accumulation, preserved mineral quantity, and led to increased E/H ratio in females. Taken together, these results highlight the complex, multi-scale and sex-dependent relationships between bone quality and function under overweightness, and identifies RAGE-controlled glycoxidation as a target to potentially preserve matrix quality and mechanical integrity.

Effects of homoarginine supplementation on heart and skeletal muscle of rats with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with left ventricular stiffness, impaired diastolic relaxation, and severe exercise intolerance. Decreased homoarginine (hArg) levels are an independent predictor of mortality in cardiovascular disease and correlate with impaired exercise performance. We recently reported alterations in arginine, hArg, and related amino acids in obese ZSF1 rats (O-ZSF1), with a HFpEF phenotype. Although low hArg is associated with diastolic dysfunction in humans, potential effects of hArg supplementation were not tested yet. At an age of 6weeks, 12 O-ZSF1 were randomized into two groups: (1) O-ZSF1 rats supplemented with hArg in their drinking water (sO-ZSF1) or (2) O-ZSF1 rats receiving no hArg supplementation (O-ZSF1). At an age of 32weeks, effects of primary prevention by hArg supplementation on echocardiographic, histological, and functional parameters of heart and skeletal muscle were determined. Lean ZSF1 rats (L-ZSF1) served as controls. hArg supplementation did not prevent impairment of diastolic relaxation (E/e': O-ZSF1 21±3 vs. sO-ZSF1 22±3, P=0.954, L-ZSF1 18±5) but resulted in more cardiac fibrosis (histological collagen staining: +57% in sO-ZSF1 vs. O-ZSF1, P=0.027) and increased collagen gene expression (Col1a1: +48% in sO-ZSF1 vs. O-ZSF1, P=0.026). In contrary, right ventricular function was preserved by hArg supplementation (TAPSE (mm): O-ZSF1 1.2±0.3 vs. sO-ZSF1 1.7±0.3, P=0.020, L-ZSF1 1.8±0.4). Musculus soleus maximal specific muscle force (N/cm2 ) in O-ZSF1 (30.4±0.8) and sO-ZSF1 (31.9±0.9) was comparable but significantly reduced compared with L-ZSF1 (36.4±0.7; both P<0.05). Maximal absolute muscle force (g) (O-ZSF1: 177.6±7.8, sO-ZSF1: 187.8±5.0, L-ZSF1: 181.5±7.9, all P>0.05) and cross-sectional fibre area (arbitrary units) (O-ZSF1: 1697±57, sO-ZSF1: 1965±121, L-ZSF1: 1691±104, all P>0.05) were not altered. Preservation of physiological hArg level in HFpEF may not be suited to prevent alterations in left ventricular and skeletal muscle function and structure. However, hArg supplementation may be beneficial for right ventricular function especially in pulmonary hypertension in HFpEF. We may speculate that clinically observed decreased hArg level are not the cause but the consequence of a yet unrecognized pathomechanism that underpins HFpEF.

Diet and rate of decomposition of the corpse in a human surrogate.

The decomposition of an inert body seems to depend on the physiological, biological and physical characteristics of the corpse. The effect of these, especially of extra-biological mechanisms, on the rate of decomposition of the corpse does not seem to be sufficiently explored. The present work proposes to examine the influence of the type of feeding on the rate of cadaver decomposition in a human surrogate. It is based on a sample of four corpses of juvenile male pigs of the species Sus scrofa domesticus, three of which are experimental and one is a control aged 12weeks and having a mass between 19 and 24kg. The three experimental pigs were fed an energetic, construction and functional diet respectively. The control was fed a general diet. These different carcasses are exposed to the open air on four similar sites. The experiment is repeated twice, according to the protocol that guided the initial experiment conducted on comparable sites (eight cadavers, six experimental and two control). The measurement of the pigs' diet was done through a questionnaire. The mass of the decomposing carcass was explored by a specific tool, in this case, the weighing device. The results show that the rate of decomposition of the cadaver of pigs fed a general diet is higher than that of the cadavers of their counterparts fed construction, functional or energy diets. The type of diet would therefore influence the rate of decomposition of the cadaver of a human surrogate.

Prenatal Buprenorphine/Naloxone or Methadone Use on Neonatal Outcomes in Michigan.

BackgroundMaternal opioid exposure during pregnancy has various effects on neonatal health. Buprenorphine/naloxone and methadone are examples of medications for opioid use disorder (MOUD) used for the treatment of opioid use disorder (OUD). Research comparing the impacts of these MOUD modalities on neonatal outcomes when used to treat pregnant people with OUD remains limited. We evaluated the differences in outcomes between neonates with in-utero exposure to buprenorphine/naloxone versus methadone.MethodologyWe performed a retrospective cohort chart review between October 15, 2008, and October 15, 2019, evaluating mother/neonate dyads at two medical centers in Michigan. The charts of female patients, aged 18+, with OUD and buprenorphine/naloxone or methadone treatment, were examined. The charts of the corresponding neonates were also examined. Multiple regression analysis was performed.ResultsIn total, 343 mother/infant dyads were included: 99 patients were treated with buprenorphine/naloxone and 232 patients were treated with methadone. The buprenorphine/naloxone group had significant differences in maternal age, hepatitis status, asthma, gestational age in weeks, neonatal intensive care unit (NICU) length of stay (LOS), neonatal opioid withdrawal syndrome (NOWS) peak score, birth head circumference, and birth weight compared to the methadone group at baseline. Adjusted multivariable regression analysis demonstrated neonates with exposure to buprenorphine/naloxone had a NOWS peak score 3.079 points less (95% confidence interval (CI): -4.525, 1.633; p = 0.001) and NICU LOS 8.955 days less (95% CI: -14.399, -3.511; p = 0.001) than neonates exposed to methadone.ConclusionsNeonates with in-utero exposure to buprenorphine/naloxone had significantly lower NOWS scores and shorter NICU LOS compared to neonates with in-utero exposure to methadone. These findings demonstrate that buprenorphine/naloxone is potentially a more favorable treatment for the reduction in metrics representing adverse neonatal outcomes in pregnant people with OUD than methadone.

Carcass characteristics and meat quality assessment in different quail lines fed on canola seed supplemented diets

The effect of dietary supplementation with canola seed on carcass and meat quality characteristics in three quail lines was studied. Ninety quails aged 4-weeks were selected from three lines (white, black and brown) and randomly allocated to 3 feeding groups. One group was fed a basal diet as control, while the other two groups were fed on basal diet with 1 or 3% canola seed supplementation. Quails were slaughtered at 10 weeks of age. At 24 h postmortem, breast and thigh meat samples were separated; vacuum packaged and stored at -40°C until meat quality analyses. Results showed that carcass characteristics did not differ (P&gt;0.05) between dietary treatments. However, the inclusion of canola seed increased (P&lt;0.05) the concentration of total omega-3 fatty acid in meat and decreased widely the omega-6: omega-3 ratio compared to the control diet. Feeding 3% canola seeds decreased the level of malondialdehyde (MDA) in the breast and thigh muscles of quails at day 5 of post-mortem. Regardless of dietary treatments, no carcass and meat quality characteristics except carcass weight differed between 3 quail lines. Brown quails exhibited significantly higher (P&lt;0.05) carcass weight than white and black ones. These results indicate that feeding canola seed might modify meat fatty acid profile with better shelf life during postmortem aging. Likewise, due to high carcass weight, brown quail lines may be preferred for meat production purposes.

Irisin/FNDC5 influences myogenic markers on skeletal muscle following high and moderate-intensity exercise training in STZ-diabetic rats.

In the present study, we investigated the effects of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) on irisin and expression of myogenic markers (paired box 7 (Pax7), myogenic differentiation 1 (MyoD), myogenin) in skeletal muscle of diabetic rats. Eighty-four male Wistar rats (6weeks of age) were randomly divided into seven groups (n = 12): basic control (Co Basic), 8weeks control (Co 8w), diabetes mellitus (DM), HIIT, DM + HIIT, MICT, and DM + MICT groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ). The protocol was characterized by running on a rodent treadmill with moderate intensity (60-70% ), 60min per session, 5days/week, for 6weeks. HIIT consisted of six 3-min runs at a high intensity (80-90% ) alternated with 2-min running at low intensity (50% ), 30min per session, 5days/week, for 6weeks. Results showed that DM decreased myoblast markers compared to Co Basic and Co 8w groups. Fibronectin type III domain-containing protein 5 (FNDC5) mRNA decrease was correlated with myoblast markers (Pax7 r = 0.632, p = 0.027; MyoD r = 0.999, p = 0.001; myogenin r = 1.000, p = 0.001) in DM group. DM + MICT significantly increased gene expression of MyoD, myogenin, and FNDC5 compared to DM and DM + HIIT. The results also showed that the intensity and duration of exercise on the treadmill were effective in stimulating irisin and myogenic markers after DM.

Effects of on-farm hatching on short term stress indicators, weight gain, and cognitive ability in layer chicks

Layer chicks are usually transported early in life, experiencing immediate post-hatch food and water deprivation and various transport-related stressors with potentially negative long-term consequences for learning, cognition and welfare. In contrast, as chicks are only temporarily exposed to these stressors, the experienced stress could be sub-chronic which may improve cognitive flexibility. The aim of this exploratory study was therefore to investigate the acute and long-term effects of on-farm hatching (OFH) compared to conventional hatching. Dekalb White layer chicks were subjected to either OFH (n = 47) with ad libitum access to feed and water or temporary post-hatch resource deprivation and eight hour transport (RDT; n = 42). Physical and behavioural measures were collected to examine short-term effects of the treatment procedures. To determine longer term effects, treatment differences in learning and cognitive flexibility were assessed in a Y-maze using several paradigms (reversal, attentional-shift, extinction) between 4 and 12 weeks of age (WOA). Compared to OFH chicks, RDT had: greater corticosterone levels after transport (F1,19 =8.15, p = 0.01, RDT (16.24 ± 1.20 ng/mL) vs. OFH (8.13 ± 1.20 ng/mL) and post-recovery (F1,19 =4.93, p = 0.04; RDT (11.69 ± 1.35 ng/mL) vs. OFH (5.31 ± 1.37)), and lower body mass after resource deprivation and transport (F2258 =9.7, p < 0.001, RDT (33.14 ± 0.33 g) vs. OFH (37.62 ± 0.28 g)). Performance of activity behaviours (foraging, drinking, resting, wing-assisted running) after transport exhibited treatment by time interactions. Additionally, a tendency for OFH being heavier than RDT chicks was observed up to 11 WOA. The majority of birds learned the initial association in the Y-maze between a reward and location (77% of n = 19 RDT and n = 29 OFH chicks) or light stimulus (91% of n = 12 RDT and n = 11 OFH chicks). Subsequently, a number of chicks reached the learning criterion in the location reversal (24% of n = 13 RDT and n = 24 OFH chicks) and the light-to-location attentional-shift (47% of n = 11 RDT and n = 10 OFH chicks), and most of these chicks succeeded in the following extinction paradigm (80% of n = 3 RDT and n = 7 OFH chicks). No treatment effects were detected in any phase of cognitive testing. In conclusion, treatment affected behaviour and health parameters suggesting RDT animals were recovering from resource deprivation and transport. Continued treatment differences in body mass throughout rearing demonstrated long term effects as well although no effects on initial learning and cognitive flexibility were identified. Future work is needed to determine what mechanisms are responsible for the observed health and behavioural differences.

Anticoccidial Vaccination Is Associated with Improved Intestinal Health in Organic Chickens.

Simple SummaryIn recent years, the number of organic chicken farms has increased. Chickens can be infected by single-cell parasites, coccidia, which cause lesions in the lining of the intestine leading to poor growth and sometimes death (coccidiosis). This infection can also lead to overgrowth in the intestine of a bacterium, Clostridium perfringens, that may cause further damage (necrotic enteritis). Prevention is often achieved by adding substances in the feed that will slow down the development of parasites and bacteria, but this is not allowed in organic farming. The aim of this study was to investigate if vaccination against coccidia can prevent these diseases in organic chickens. Vaccinated chickens developed milder gut lesions, had fewer and less damaging C. perfringens, and had similar or higher body weight compared to unvaccinated chickens six weeks after vaccination. No deaths from coccidiosis or necrotic enteritis occurred among vaccinated chickens while some unvaccinated chickens died from these diseases. We conclude that vaccination against coccidia benefits organic chickens. This study provides knowledge supporting further development of the organic chicken industry. The results are also of relevance to the management of coccidiosis and necrotic enteritis in conventional broilers.Eimeria spp. and Clostridium perfringens (CP) are pathogens associated with coccidiosis and necrotic enteritis (NE) in broiler chickens. In this study we evaluated the effect of anticoccidial vaccination on intestinal health in clinically healthy organic Ross 308 chickens. On each of two farms, one unvaccinated flock (A1 and B1) was compared to one vaccinated flock (A2 and B2) until ten weeks of age (WOA). Faecal oocysts were counted weekly, and species were identified by PCR (ITS-1 gene). Lesion scoring, CP quantification and PCR targeting the CP NetB toxin gene were performed at three, four, and six WOA and chickens were weighed. Necropsies were performed on randomly selected chickens to identify coccidiosis/NE. Oocyst shedding peaked at three WOA in all flocks. Later oocyst shedding (E. tenella/E. maxima) in unvaccinated flocks at 5–7 WOA coincided with coccidiosis/NE. Although results differed somewhat between farms, vaccination was associated with lower intestinal lesion scores, reduced caecal CP counts, lower proportions of netB-positive CP, lower body weight at three–four WOA, and similar or slightly increased body weight at six WOA. In conclusion, the intestinal health of organic broilers can benefit from anticoccidial vaccination when oocyst exposure levels are high.

Mouse models of NADK2 deficiency analyzed for metabolic and gene expression changes to elucidate pathophysiology.

NADK2 encodes the mitochondrial form of nicotinamide adenine dinucleotide (NAD) kinase, which phosphorylates NAD. Rare recessive mutations in human NADK2 are associated with a syndromic neurological mitochondrial disease that includes metabolic changes, such as hyperlysinemia and 2,4 dienoyl CoA reductase (DECR) deficiency. However, the full pathophysiology resulting from NADK2 deficiency is not known. Here, we describe two chemically induced mouse mutations in Nadk2-S326L and S330P-which cause severe neuromuscular disease and shorten lifespan. The S330P allele was characterized in detail and shown to have marked denervation of neuromuscular junctions by 5weeks of age and muscle atrophy by 11weeks of age. Cerebellar Purkinje cells also showed progressive degeneration in this model. Transcriptome profiling on brain and muscle was performed at early and late disease stages. In addition, metabolomic profiling was performed on the brain, muscle, liver and spinal cord at the same ages and on plasma at 5weeks. Combined transcriptomic and metabolomic analyses identified hyperlysinemia, DECR deficiency and generalized metabolic dysfunction in Nadk2 mutant mice, indicating relevance to the human disease. We compared findings from the Nadk model to equivalent RNA sequencing and metabolomic datasets from a mouse model of infantile neuroaxonal dystrophy, caused by recessive mutations in Pla2g6. This enabled us to identify disrupted biological processes that are common between these mouse models of neurological disease, as well as those processes that are gene-specific. These findings improve our understanding of the pathophysiology of neuromuscular diseases and describe mouse models that will be useful for future preclinical studies.

Deletion of microRNA-183-96-182 Cluster in Lymphocytes Suppresses Anti-DsDNA Autoantibody Production and IgG Deposition in the Kidneys in C57BL/6-Faslpr/lpr Mice.

Dysregulated miRNAs have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Our previous study reported a substantial increase in three miRNAs located at the miR-183-96-182 cluster (miR-183C) in several autoimmune lupus-prone mice, including MRL/lpr and C57BL/6-lpr (B6/lpr). This study reports that in vitro inhibition of miR-182 alone or miR-183C by specific antagomirs in activated splenocytes from autoimmune-prone MRL/lpr and control MRL mice significantly reduced lupus-related inflammatory cytokines, interferon-gamma (IFNγ), and IL-6 production. To further characterize the role of miR-182 and miR-183C cluster in vivo in lupus-like disease and lymphocyte phenotypes, we used hCD2-iCre to generate B6/lpr mice with conditional deletion of miR-182 or miR-183C in CD2+ lymphocytes (miR-182−/−B6/lpr and miR-183C−/-B6/lpr). The miR-182−/−B6/lpr and miR-183C−/−B6/lpr mice had significantly reduced deposition of IgG immunocomplexes in the kidney when compared to their respective littermate controls, although there appeared to be no remarkable changes in renal pathology. Importantly, we observed a significant reduction of serum anti-dsDNA autoantibodies in miR-183C−/−B6/lpr mice after reaching 24 weeks-of age compared to age-matched miR-183Cfl/flB6/lpr controls. In vitro activated splenocytes from miR-182−/−B6/lpr mice and miR-183C−/−B6/lpr mice showed reduced ability to produce lupus-associated IFNγ. Forkhead box O1(Foxo1), a previously validated miR-183C miRNAs target, was increased in the splenic CD4+ cells of miR-182−/−B6/lpr and miR-183C−/−B6/lpr mice. Furthermore, in vitro inhibition of Foxo1 with siRNA in splenocytes from miR-182−/−B6/lpr and miR-183C−/-B6/lpr mice significantly increased IFNγ expression following anti-CD3/CD28 stimulation, suggesting that miR-182 and miR-183C miRNAs regulate the inflammatory IFNγ in splenocytes via targeting Foxo1. The deletion of either miR-182 alone or the whole miR-183C cluster, however, had no marked effect on the composition of T and B cell subsets in the spleens of B6/lpr mice. There were similar percentages of CD4+, CD8+, CD19+, as well as Tregs, follicular helper T (TFH), germinal center B (GCB), and plasma cells in the miR-183C−/−B6/lpr and miR-182−/−B6/lpr mice and their respective littermate controls, miR-183Cfl/flB6/lpr and miR-182fl/flB6/lpr mice. Together, our data demonstrate a role of miR-183C in the regulation of anti-dsDNA autoantibody production in vivo in B6/lpr mice and the induction of IFNγ in in vitro activated splenocytes from B6/lpr mice.

The effect of chronic exposure to metformin in a new type-2 diabetic NONcNZO10/LtJ mouse model of stroke.

Diabetes is an independent risk factor of stroke and previous studies have confirmed that diabetic patients and animals experience poorer clinical outcomes following stroke. In this study, we aim to determine the effect of chronic exposure of the first-line antidiabetic agent, metformin, to restore euglycemia and to impact brain cell death following stroke in a new type-2 diabetes, NONcNZO10/LtJ (RCS-10) mouse model of stroke. Male RCS-10 mice received a moderate (11%) fat diet post-weaning, at 4weeks of age, and became diabetic by 12-14weeks, thus resembling human maturity-onset diabetes. The mice received either metformin or vehicle for 4weeks before undergoing a hypoxic/ischemic (HI) insult. Blood samples were collected pre-, post-treatment, and post HI for glucose and lipid measurements, and brains were analyzed for infarct size, glial activation, neuronal cell death, and metformin-mediated adenosine monophosphate-activated protein kinase (AMPK) signaling at 48h post HI. Pretreatment with metformin maintained euglycemia for 4weeks but did not change body weight or lipid profile. Metformin treatment significantly enhanced the microglial Bfl-1 mRNA expression and showed a non-significant increase in GFAP mRNA, however, GFAP protein levels were reduced. Metformin treatment slightly increased neuronal NeuN and MAP-2 protein levels and significantly reduced overall mortality post HI but did not elicit any significant change in infarct size. The study suggests that the prolonged effect of metformin-induced euglycemia promoted the microglial activation, reduced neuronal cell death, and improved the overall survival following stroke, without any change in infarct size.

Maternal and Neonatal Outcomes in Hypertensive Disorders during Pregnancy

Context: Pregnancy is a physiological phenomenon, and each pregnancy is unique and valuable in its own way. Hypertensive diseases during pregnancy begin throughout pregnancy and disappear entirely after birth. Hypertensive disorders in pregnancy (HDP), including pregnancy-induced hypertension (HTN), chronic HTN (CHTN), (superimposed) preeclampsia, and eclampsia, are responsible for increased perinatal morbidity and mortality. Aim: The aim of this study was to investigate the prevalence and perinatal effects in women with hypertensive disease during pregnancy. Setting and Design: Hospital based cross section study was conducted on pregnant women. Methods and Materials: A hospital-based cross-sectional study was carried out from September 2019 to August 2021 on women whose pregnancies were complicated by HTN disorders. Mothers of the baby suffering from systemic diseases were excluded from the study. Statistical analysis used: Descriptive and inferential statistical analysis was conducted. Results: In the present study results the prevalence of gestational HTN at 8.49%, preeclampsia at 18.10%, severe preeclampsia at 8.75%, and CHTN was 2.28%. It was shown that the prevalence of hypertensive disease is 38%. A significant difference was found between the maternal age group of mothers suffering from HTN disorders during pregnancy with mean gestational age in weeks F = 124.6477, P = 0.0001 at a 5% level. Furthermore, a significant statistical difference was observed with different maternal age groups having different mean Apgar scores at 1 min with F = 81.0233, P = 0.0001. Conclusion: Prenatal HTN is one of the leading causes of maternal and neonatal death. Despite having all of the resources and several government programs in both urban and rural areas, many women suffer from HDP in both locations (rural and urban). Hence, management, as well as awareness among pregnant women regarding hypertensive diseases in pregnancy, is required.

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.