Weeks Of Age Research Articles

Histomorphological characteristics of keel bone maturation and keel bone fractures in laying hens.

The keel bone in laying hens is prone to fractures, especially on the caudal third of the keel, which is also the last part to ossify. Keel bone fractures (KBF) typically occur between 25 and 50 weeks of age (WOA). However, the keel is fully ossified at around 40 WOA, suggesting fractures can occur before ossification is complete. To better understand the relationship between KBF and ossification, this descriptive study examined keel bone morphology during maturation. Keel bones from 50 commercial aviary housed Dekalb White laying hens were collected at 10 timepoints from 17-53 WOA and prepared for histological analysis. The samples were stained with haematoxylin and eosin and Safranin O to show cartilage, ossification, bone tissue, and KBF. The results indicated an ossification process similar to endochondral ossification. The degree of ossification varied between individuals of the same age. The age at complete ossification varied from 28-49 WOA. None of the keels from hens aged 53 WOA were fully ossified. Cartilage canals were present in the keel cartilage. Medullary bone was observed in all age groups. Most fractures lacked tissue morphologies typical of high-impact collisions, suggesting the need for further research into the underlying causes. This is the first study to detail keel bone histomorphology in commercial laying hens, providing baseline data for future research.

Delayed macular development in preterm infants with spontaneously regressed retinopathy of prematurity

PurposeTo evaluate the macular development in preterm infants with spontaneously regressed retinopathy of prematurity (ROP) utilizing handheld spectral domain optical coherence tomography (SD-OCT) during the early postnatal period.DesignA cross-sectional observational study.MethodsUsing handheld SD-OCT, OCT images were acquired in non-sedated infants ages about 37 weeks(w) post-menstrual-age (PMA = gestational age in weeks + chronological age). Central foveal thickness (CFT), mean parafoveal thickness (PT, mean of the temporal and nasal-lateral retinal thickness 1000 μm from the foveal center), the thickness of inner retina layers (IRL) and outer retina layers (ORL) of the foveal center and parafoveal, the depth of the macular fovea (FD), and the angle of the macular fovea (FA) were measured and analyzed.ResultsIn contrast to the infants without ROP (group 1), OCT images of the infants with spontaneously regressed ROP (group 2) were more immature. The FD of Group 2 was shallower than Group 1 (P < 0.05); CFT and the foveal center IRL (FIRL) of Group 2 were thicker than Group 1 (P < 0.05); conversely, PT and the mean parafoveal IRL (PIRL) of Group 2 were thinner than Group 1 (P < 0.05); FA of Group 2 was bigger than Group 1 (P < 0.05); however, there was no significant difference in the foveal center ORL (FORL) and the mean parafoveal ORL (PORL) between Groups 1 and 2 (P > 0.05). Furthermore, in preterm infants, ROP was moderately correlated with FD, CFT, PT, FIRL, and PIRL (P < 0.05).ConclusionsThe spontaneously regressed ROP resulted in immature macular development in the early postnatal period. The inner retinal layers mainly contribute to this but not the outer retinal layers, indicating that the macular fovea’s inner and outer retina layers developed asynchronously. ROP is an influential factor in macular development and maturation. This may be associated with the higher probability of visual impairment in children with a history of spontaneous regression of ROP at a prior time.

Polydatin retards the progression of osteoarthritis by maintaining bone metabolicbalance and inhibiting macrophage polarization.

Polydatin (PD), also known as tiger cane glycoside, is a natural compound extracted from the Japanese knotweed plant, which is often referred to as white resveratrol. It exhibits anti-inflammatory, antioxidant, and anti-apoptotic effects in the treatment of various diseases. However, the potential molecular mechanisms of PD in osteoarthritis have not been clearly elucidated. Anterior cruciate ligament transection (ACLT) surgery was performed to establish an osteoarthritis animal model. Female mice at the age of 12weeks were intraperitoneally injected with different concentrations of PD (20 and 40mg/kg). In vitro models were established by isolating mouse articular chondrocytes, which were subsequently treated with lipopolysaccharide or IL-1β for 24h for subsequent experiments. In addition, different concentrations of PD were administered for 12h. Morphological changes were observed by toluidine blue staining, joint bone metabolism changes were observed by tartrate-resistant acid phosphatase staining, immunohistochemistry was used to observe the expression levels of inflammatory factors and extracellular matrix. MicroCT analysis was conducted to assess changes in the microstructure of subchondral bone trabeculae, and Western blot was performed to measure the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and markers of M1 polarization in macrophages. PD significantly delays the progression of osteoarthritis induced by ACLT, effectively inhibits IL-1β-induced joint inflammation, bone metabolic remodeling and extracellular matrix degradation. In addition, paeoniflorin markedly suppresses the transmission of the NF-κB signaling pathway and reverses M1 polarization in macrophages induced by IL-1β. Taken together, PD might be a potential therapeutic agent for the prevention and treatment of osteoarthritis.

Traditional pediatric massage enhanced the skeletal muscle mass in OVA-exposed adolescent rats via regulating SCFAs-FFAR2-IGF-1/AKT pathway.

This study aimed to investigate the potential relation between the retarded growth of skeletal muscle (SM) and dysbiosis of gut microbiota (GM) in children with asthma, and to explore the potential action mechanisms of traditional pediatric massage (TPM) from the perspective of regulating GM and short-chain fatty acids (SCFAs) production by using an adolescent rat model of asthma. Male Sprague-Dawley rats aged 3weeks were divided randomly into the 5 groups (n=6~7) of control, ovalbumin (OVA), OVA + TPM, OVA + methylprednisolone sodium succinate (MP) and OVA + SCFAs. Pulmonary function (PF) was detected by whole body plethysmograph, including enhanced pause and minute ventilation. Airway allergic inflammation (AAI) status was assessed by concentrations of OVA-specific immunoglobulin E in plasma, interleukin (IL)-4 and IL-1β in bronchoalveolar lavage fluid via ELISA assay. SM mass was assessed by using cross-sectional areas of diaphragm muscle and gastrocnemius via hematoxylin and eosin staining. GM and SCFAs production were detected by 16S rDNA sequencing and GC-MS, respectively. The protein and gene expressions of free fatty acid receptor 2 in SM were detected by using immunohistochemical staining and qRT-PCR, respectively. qRT-PCR was used to detect other relative gene expressions that were closely related with SM mass. The activity of insulin-like growth factor-1 (IGF-1)/protein kinase B (PKB/AKT) pathway in SM was detected by western blotting test. OVA exposure caused obvious AAI and poor PF in adolescent rats. OVA-exposed adolescent rats had a retarded growth of SM mass and inhibited activity of IGF-1/AKT pathway, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, along with alleviating AAI and improving PF. TPM activated IGF-1/AKT pathway in SM, which was closely related with correcting GM dysbiosis, enhanced SCFAs production and FFAR2 expressions. The retarded growth of SM mass and inhibition of IGF-1/AKT pathway existed in OVA-exposed adolescent rats, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, at least, partially via regulating GM, enhancing SCFAs production and activating FFAR2-IGF-1/AKT pathway.

A comparation of three different anti-VEGF drugs in development of persistent avascular retina in premature children

Our current prospective cross-sectional study aimed to investigate the effect of anti-vascular endothelial growth factor (VEGF) drugs used in the treatment of retinopathy of prematurity on retinal maturation and persistent avascular retina (PAR). Retinal imaging was performed with Optos confocal laser ophthalmoscopy for 100 patients aged 4 to 8 years who were screened and treated for retinopathy of prematurity (ROP) during the neonatal period. The ROP examination findings (stage and zone) and treatment history (age in weeks at time of treatment and anti-VEGF drug used) from the neonatal period were reviewed. Retinal vascularization was assessed in fundus images using the green filter on the Optos device and the presence of PAR was evaluated by two investigators. Relationships between the rate of PAR, age in weeks at time of treatment, and type of anti-VEGF drug used were analyzed statistically. The study included 196 eyes of 100 patients. Sixty-four eyes were analyzed in Group 1 (no ROP), 23 eyes in Group 2 (ROP, no treatment), and 108 eyes in Group 3 (treated group; anti-VEGF treatment of ROP with ranibizumab, bevacizumab, or aflibercept). The number of eyes with PAR in these groups was 2 (3.7%), 4 (17.4%), and 45 (41.7%), respectively. PAR was detected in 30 of 44 eyes treated with aflibercept. The rate of PAR was higher after aflibercept treatment (68.2%) with statistical significance (p = 0.000). This study showed that the prevalence of PAR differs between anti-VEGF drugs. Patients treated with aflibercept have a higher risk of late complications and should be followed closely.

The effect of ovariectomy, 17β-estradiol treatment, and progesterone treatment on dopaminergic regulation of prepulse inhibition in adult and adolescent female mice.

The aim of the present study was to investigate the role of ovarian hormones on dopaminergic regulation of prepulse inhibition (PPI), a measure of sensorimotor gating deficient in schizophrenia and other psychiatric illnesses. Either in adulthood (11weeks of age) or adolescence (5weeks of age), female mice underwent ovariectomy (OVX) and were implanted with 17β-estradiol, progesterone, or a combination of these hormones. All mice were tested in adulthood for the acute effect of the dopamine receptor agonist, apomorphine, on PPI. Apomorphine treatment reduced PPI in intact mice and this effect was blocked after OVX in adulthood. A low dose implant of 17β-estradiol prevented this OVX effect and reinstated apomorphine-induced PPI disruption. Following adolescent OVX, the effect of apomorphine was not altered and it significantly reduced PPI in adulthood. A low dose implant of 17β-estradiol following adolescent OVX effect blocked apomorphine-induced PPI disruption in adulthood. Apomorphine had no effect on PPI in any of the mice treated with the high dose of 17β-estradiol or a combination of low-dose 17β-estradiol and progesterone, irrespective of treatment age, suggesting an antipsychotic action. Apomorphine tended to disrupt PPI in mice treated with progesterone only, irrespective of age of OVX. These results suggest that in adult mice, circulating 17β-estradiol and progesterone play an important role in dopaminergic regulation of PPI. This role may develop during adolescence as similar effects of OVX and ovarian hormones were not observed following interventions in 5-week old mice. Our results also confirm and extend previous evidence that 17β-estradiol may have antipsychotic properties.

Comparison of the Efficacy of Mycoplasma gallisepticum Vaccine Programs in Chickens

ABSTRACT The efficacy of two Mycoplasma gallisepticum commercially available vaccines administered singly or in combination was evaluated in two trials; in both trials, specific-pathogen-free (SPF) chickens were vaccinated with the live attenuated F-strain vaccine at 5 weeks of age (WOA), an inactivated M. gallisepticum bacterin at 9 and 13 WOA, or both vaccines. In the first trial, groups of vaccinated birds, along with controls, were challenged via aerosol with virulent R-strain at 22 and 41 weeks of age. All of the vaccine programs evaluated showed a statistically significant reduction in colonization with the challenge strain following challenge at either timepoint. However, only the programs including the live vaccine also showed significant protection from respiratory lesions and ovarian regression; and although there were numerical differences indicating benefits of a combined (live + bacterin) program, the addition of bacterins did not enhance (or reduce) the efficacy of the F-strain vaccine in a statistically significant manner (P ≤ 0.05). In the second trial, groups of vaccinated birds, along with controls, were challenged via aerosol with different doses of virulent M. gallisepticum R-strain at 17 weeks of age. Both vaccination programs in this trial (live only and live + bacterin) resulted in significant protection against challenge strain colonization and air sac lesions (P ≤ 0.05); In addition, the live + bacterin program showed significantly improved results with respect to colonization with the challenge strain as well as protection from air sac lesions compared to the live vaccine alone (P ≤ 0.05).

Post-Traumatic Stress in Mothers of Children Having Complex Cardiac Surgery Early in Life.

To determine: (i) frequency of probable post-traumatic stress disorder (PTSD) in mothers of infants after complex cardiac surgery (CCS), (ii) predictors of probable PTSD, and (iii) impact on child neurodevelopment. The Impact of Event Scale-Revised (IES-R) was administered to 60 mothers of infants ≥ 6months after CCS at ≤ 6weeks of age. The IES-R measures response to a specific traumatic event: Scores < 24, no concern; 24-32, clinical concern; and ≥ 33, probable diagnosis of PTSD. Post-survey childhood outcomes obtained at 21-months used Bayley Scales of Infant and Toddler Development-Third Edition. Multiple logistic and linear regressions were used to predict high IES-R scores from peri-operative and demographic variables and determine association between maternal IES-R scores and outcomes, reported as Odds Ratio (OR) and Effect Size (ES) with 95% Confidence Intervals (95% CI). IES-R scores ≥ 33 occurred in 14/60 (23%) of mothers. Significant risk factors for IES-R ≥ 33 were days of ventilation after first surgery, OR 1.149 (95% CI 1.037, 1.273), p = 0.008, and birth weight z-scores, OR 0.352 (0.140, 0.881), p = 0.026. Bayley cognitive, language, and motor scores were significantly lower for children whose mothers had IES-R ≥ 33. The IES-R was independently associated with cognitive, ES -0.23 (95%CI -00.39, -00.08), p = 0.036 and language, ES -00.17 (95%CI -00.33, -00.06), p = 0.043 scores. Probable PTSD occurred in 23% of mothers ≥ 6month after discharge of their infant following CCS. Toddlers of mothers with probable PTSD had lower cognitive and language scores suggesting a relation between PTSD and development requiring further study.

Loss of Sult1a1 reduces body weight and increases browning of white adipose tissue.

Overweight and obesity affects millions of individuals worldwide and consequently represents a major public health concern. Individuals living with overweight and obesity have difficulty maintaining a low body weight due to known physiological mechanisms which prevent further weight loss and drive weight regain. In contrast, mechanisms which promote low body weight maintenance receive less attention and are largely unknown. To uncover these intrinsic mechanisms, we investigated a human cohort of constitutionally thin (CT) individuals which maintain a low body weight and are resistant to weight gain despite exposure to an obesogenic environment. To identify novel genes that contribute to low body weight maintenance, we performed transcriptomics on adipose tissue biopsies collected from CT and normal body weight (NBW) individuals and identified sulfotransferase 1A1 (SULT1A1) as a target for further investigation in mice. Sult1a1 knockout (KO) mice were fed a standard diet to assess the impact of Sult1a1 deletion on metabolic traits. To determine if high-fat feeding recapitulated the CT weight gain resistance phenotype, Sult1a1 KO mice were fed a high-fat diet for 13-weeks. A subset of wild-type and Sult1a1 KO mice from the standard diet were further analyzed for characterization of adipose tissue respiratory capacity. In comparison to NBW controls, adipose tissue from CT individuals expresses less SULT1A1. Sult1a1 KO mice weigh 10% less at the end of the study period and on a high-fat diet, Sult1a1 KO mice tended to gain less weight and had reduced fat mass at 14-weeks of age. These changes were associated with reduced fasting insulin and lessened adipose tissue inflammation and fibrosis. Subcutaneous adipose tissue from Sult1a1 KO mice on a standard chow diet had elevated leak respiration, uncoupling protein 1 (UCP1) expression and increased expression of a mitochondrial marker, VDAC, associating Sult1a1 deletion to adipose tissue browning. Our results associate Sult1a1 deletion with a tendency for lower body weight through remodeling of white adipose tissue towards a brown phenotype. The presence of UCP1, the expression of an additional mitochondrial protein and increased respiratory capacity suggest browning of the subcutaneous adipose tissue depot of Sult1a1 KO mice.

Re-evaluating the timing of sequential cranial ultrasound screening in very preterm infants for predicting neurodevelopmental outcomes.

Accurate and early prediction of neurodevelopmental impairment is a crucial endeavor in caring for very preterm infants (<31weeks' gestation). Sequential cranial ultrasound is the standard of care for the evaluation of preterm brain injury. However, there is no consensus on the timing and frequency of ultrasound screening. At Izaak Walton Killam (IWK) Health Centre, Halifax, Canada, four-time points for routine ultrasound of very preterm infants are performed at weeks 1, 2, 6, and term age. The hypothesis behind this work is that a three-time-point model will be appropriate for neurodevelopmental impairment prognostication. In this retrospective cohort, all very preterm infants (220-306weeks) born between January 2004 and December 2018 with a neurodevelopmental assessment at 36months corrected age were included. Three prediction models of neurodevelopmental impairment were compared: 1. A reference model including the gestational age, infant sex, and 2-week and 6-week ultrasound 2. A model including the gestational age, infant sex, and 6-week ultrasound 3. A model including the gestational age, infant sex, and 2-week ultrasound RESULTS: Of 786 eligible preterm infants born during the study period, 656/786 survivors were included in the analysis (mean gestational age 275weeks, mean birth weight 1,133g, and 55% male infants). At 36months of corrected age, 30% developed neurodevelopmental impairment. All three models provided comparable discrimination areas under the curve (AUC) of neurodevelopmental impairment at 36months of corrected age. Both the 6-week and the reference model had similar AUC of 0.68 (95% CI 0.63-0.72) and were not noticeably different from the 2-week model (AUC 0.66 (95% CI 0.61-0.70)). The 6-week model provided the best prediction with the lowest Akaike information criterion (AIC) of 766 for the 6-week-only model, AIC 769 for combined weeks 2 and 6 (reference model), and AIC 784 for the 2-week-only model. In this cohort of very preterm infants, a model including 6-week ultrasound only was comparable to a reference model combining 2-week and 6-week ultrasound and showed nearly identical predictive performance of neurodevelopmental impairment at 36months corrected age across a broad set of metrics; thus, it is redundant to do both the 2-week and 6-week ultrasound. Late ultrasound at 6weeks of age provided comparable diagnostic and prognostic information to a reference model combining 2-week and 6-week ultrasound and, if anything, was slightly superior to the 2-week ultrasound model, across a broad set of metrics. The 2-week ultrasound can be eliminated with no impact on the prediction of neurodevelopmental impairment at 36months, promoting prudent resource allocation and stewardship in healthcare.

Investigating long‐term, progressive cerebral microvascular alterations in late‐onset Alzheimer's disease using APOE4 transgenic mice

AbstractBackgroundRecent studies show apolipoprotein E4 (APOE4), the strongest known genetic risk factor for late‐onset Alzheimer’s disease, is associated with vascular dysfunctions such as blood‐brain barrier breakdown, in both animal models and humans. However, there is a lack of understanding on how vascular alterations progress with age in APOE4.MethodHuman APOE4 (m/f, n=10 per group) and APOE3 targeted replacement mice (m, n=10) were used to investigate temporal dynamics of long‐term, progressive cerebral microvascular alterations in APOE4. we acquired a set of imaging data including optical coherence tomography (OCT) angiogram and doppler OCT to quantify relative changes in pial and penetrating vessels with age (starting at 13 weeks of age (WOA) and repeated every 4 weeks until 57 WOA). For assessing cognitive function, novel object location test (NOL) was used and performed every 4 weeks starting from 17 WOA.ResultWe compared the rate of change with age (RCA) values between the groups to find the effects of APOE4 and female. In pial vessel diameter, both APOE4‐m and APOE4‐f groups showed vessel diameter decreasing with age at a rate of 2.7 and 3.1% per month, respectively. In contrast, the control group (APOE3‐m) exhibited a slight increase in vessel diameter at a rate of 1.0% per month. When compared between groups based on RCA values, the age of significance (AOS) for the effect of APOE4 was 28 WOA. Adding the effect of female with APOE4, the result showed an earlier AOS of 26 WOA. In penetrating vessels (diameter/flow change in arterioles/venules), a similar trend was observed with both APOE4 groups exhibits more rapid decreasing RCAs and earlier AOS (27 WOA as earliest) than APOE3. More importantly, these AOS values were much faster than cognitive decline (51 WOA).ConclusionWe found vascular alterations in both pial and penetrating vessels occurred earlier than cognitive decline, being generally greater and earlier in female APOE4 than male APOE4 mice. This female effect in APOE4, although the underlying mechanisms behind such finding is beyond the scope of this study, could still provide valuable insights on understanding vascular dysfunction in sex‐dependent manner.

Electrical impedance myography detects progressive pathological alterations in the hindlimb muscle of the PMP22-C3 mice, an animal model of CMT1A.

Charcot-Marie-Tooth type 1A (CMT1A) is the most common inherited peripheral dysmyelinating neuropathy. Although lower limb muscle weakness is the most important factor affecting the quality of life of patients with CMT1A, existing clinical measures for its evaluation have limitations, including low sensitivity in detecting disease progression. Electrical impedance myography (EIM) is a newer tool that enables noninvasive evaluation of muscle state by measuring muscle composition, and potentially supports the evaluation of neuromuscular disease progression and treatment effects. To determine the potential of EIM as a CMT1A biomarker, we obtained natural history data for EIM from the gastrocnemius muscle of the PMP22-C3 mice, an animal model of CMT1A. Alterations in the EIM parameters, weak hindlimb grip strength, decreased muscle fiber size, and changes in the mRNA expression of genes related to neuromuscular junction dysfunction were found. These changes were more pronounced at later stages (12 and 18weeks of age) than at earlier stage (6weeks of age), indicating that EIM can detect disease progression in PMP22-C3 mice. Our preclinical findings support the use of EIM as a potential translational biomarker for assessing progressive changes in the pathological muscle state in CMT1A.

Timing, risk factors, and causes of foetal and preweaning lamb mortality in lowland production systems involving a range of ewe genotypes.

Reducing lamb mortality has production, economic and animal welfare benefits. The timing and causes of death and associated risk factors were investigated in a study conducted over 2 consecutive years (involving 1103 and 1038 ewes in 2017 and 2018, respectively) in three prolific (average litter size 1.91) indoor-lambing, lowland flocks (in Ireland) that consisted of a range of genotypes, managed in grass-based systems of production. Data were collected from all foetuses and lambs that died (between∼120days gestation and weaning at 14weeks of age); 221 cases in 2017 and 241 cases in 2018. All cases were submitted to a Regional Veterinary Laboratory for necropsy examination using standardised protocols that were developed in advance of case submissions. The majority (60%) of lamb mortality occurred prior to or within 24h of birth: 46% at or prior to birth and 14% within the first 24h. Infection (32%) and dystocia (20%) accounted for over half of the mortality. Chlamydia abortus was detected more often in lambs from 2-year-old ewes lambing for the first time than in lambs from older ewes. Dystocia accounted for a statistically significant higher proportion of deaths among purebred lambs born to Texel ewes (49.4%, 95%CI (confidence interval) 36.0 - 62.9) compared to purebred lambs born to Belclare ewes (12.8, 95%CI 2.2 - 23.5). More lambs failed to yield a diagnosis of the cause of death when born to Belclare ewes (29.2%, 95%CI 17.8 - 40.6) than to Suffolk-X ewes (7.4%, 95%CI 0.1 - 14.8). About one-third of lamb mortality cases were adjudged to be preventable through more consideration of management factors during pregnancy, parturition and early postpartum. The use of good hygiene practices at lambing time and optimising lamb birth weight should reduce the level of preweaning lamb mortality in indoor lambing flocks.

Pregnancy dating: Determining gestational age through fetal kidney length-what do we observe?

Accurate gestational age is crucial for obstetric care, pregnancy management, and preterm labor decisions. Ultrasound, based on fetal biometric parameters, is a reliable method for this purpose. This study aims to estimate gestational age in the third trimester using ultrasonographic methods, focusing on fetal kidney length. Gestational age is estimated in the third trimester by measuring fetal kidney length and comparing it with gestational age derived from other biometric parameters (bi-parietal diameter, head circumference, abdominal circumference, and femur length) and the last menstrual period (LMP). A nine-month prospective study was conducted Kozhikode, Kerala, from September 2016 to May 2017. The study involved 200 women in their third trimester of pregnancy, utilizing third-trimester ultrasound to measure and document kidney length along with other biometric parameters (BPD, HC, AC, and FL). Subsequently, the collected data was reviewed and analyzed.: The study revealed a strong positive correlation between fetal kidney lengths (FKL) measured in millimeters and gestational age in weeks during the third trimester. The correlation was significant, with a Pearson's correlation coefficient of 0.87 (p &amp;#60; 0.001). Additionally, FKL exhibited positive correlations with other variables, including abdominal circumference (r = 0.832), head circumference (r = 0.845), bi-parietal diameter (r = 0.838), and femur length (r = 0.837). These findings demonstrated a strong Pearson’s correlation (r= 0.87-0.96, P &amp;#60;0.05) for all the biometric parameters including FKL. A linear relationship exists between fetal kidney length (FKL) and gestational age, allowing FKL to serve as an effective parameter for estimating gestational age during the third trimester. Given its positive correlation with other fetal biometric parameters such as bi-parietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL), incorporating FKL alongside these measurements enhances the accuracy of gestational dating in the third trimester. This combination of parameters improves the prediction of gestational age during this stage of pregnancy.

Determining optimal pretreatment in cardiac surgery: an experimental study.

Heart failure patients with reduced ejection fraction are currently treated with four drug combinations: angiotensin receptor/neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors, resulting in improved survival outcomes. Herein, we examined whether myocardial protection by esaxerenone or sacubitril/valsartan may present a counter-effect to the harm caused by cardioplegic arrest. Male Wistar rats fed a normal diet were orally administered esaxerenone (3mg/kg; Esax) or sacubitril/valsartan (68mg/kg; SaV) once a day for 2weeks from 6weeks of age. Age-matched, untreated male Wistar rats served as controls (Control). Isolated rat hearts were aerobically Langendorff-perfused and subjected to 2min of St Thomas' Hospital 2 cardioplegia (STH2) infusion and 28min of normothermic global ischemia followed by 60min of reperfusion. The recovery of function was measured during 60min of reperfusion. Additionally, troponin T levels were measured after reperfusion as myocardial injury. The final recovery of left ventricular developed pressure (presented as the percentage of preischemic value) in the Control, Esax, and SaV groups was 50.7 ± 6.2%, 68.5 ± 7.4%*, and 69.3 ± 14.3%*, respectively (*p < 0.05 vs. Control). Troponin T (ng per gram wet weight) levels in the Control, Esax, and SaV groups were 166.8 ± 78.1, 77.0 ± 14.6*, and 74.2 ± 36.6*, respectively (*p < 0.05 vs. Control). Oral administration of esaxerenone or sacubitril/valsartan to rats 2weeks prior to surgery enhanced the myocardial protection afforded by STH2 and may attenuate the myocardial injury caused by hyperkalemic cardioplegic arrest.

Does environmental enrichment mitigate the adverse effects of chronic low dose-rate radiation exposure on mice?

The purpose of the study was to determine whether environmental enrichments (EE) can mitigate the adverse effects of chronic low-dose-rate radiation exposure in mice. Female B6C3F1 mice were continuously exposed to 20mGyd-1 gamma-rays under specific-pathogen-free conditions since 8weeks of age for 400d. After completion of the radiation exposure, OV3121 cells, derived from an ovarian granulosa cell tumor, were inoculated subcutaneously alongside age-matched non-irradiated control mice. Irradiated mice were shown to have a significantly reduced ability to eliminate inoculated tumors. The results indicate that EE may be able to mitigate the adverse effects of low-dose-rate radiation exposure, but the effects vary greatly and are complex depending on the type of EE.

Effects of iron overload in human joint tissue explant cultures and animal models.

Osteoarthritis (OA) is a prevalent degenerative joint disease affecting over 530 million individuals worldwide. Recent studies suggest a potential link between iron overload, a condition characterised by the excessive accumulation of iron in the body, and the onset of OA. Iron is essential for various biological processes, and any disruption in its homeostasis can trigger significant health effects, including OA. This study aimed to elucidate the effects of excess iron on joint tissue and the underlying mechanisms associated with excess iron and OA development. Human articular cartilage (n = 6) and synovium (n = 4) were collected from patients who underwent total knee arthroplasty. Cartilage and synovium explants were incubated with a gradually increasing concentration of ferric ammonium citrate for 3days respectively. The effects of iron homeostasis in tissue explants were analysed using a Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). To further study the effects of iron excess on OA initiation and development, male 3-week-old Hfe-/- and 5-week-old Tfr2-/- mice, animal models of hereditary haemochromatosis were established. Littermate wild-type mice were fed a high-iron diet to induce dietary overload. All animals were sacrificed at 8weeks of age, and knee joints were harvested for histological analysis. The LA-ICP-MS analysis unveiled changes in the elemental composition related to iron metabolism, which included alterations in FTH1, FPN1, and HAMP within iron(III)-treated cartilage explants. While chondrocyte viability remained stable under different iron concentrations, ex vivo treatment with a high concentration of Fe3+ increased the catabolic gene expression of MMP13. Similar alterations were observed in the synovium, with added increases in GAG content and inflammation markers. In vivo studies further supported the role of iron overload in OA development as evidenced by spontaneous OA symptoms, proteoglycan loss, increased Mankin scores, synovial thickening, and enhanced immunohistochemical expression of MMP13, ADAMTS5, and P21 in Hfe-/-, Tfr2-/-, and diet-induced iron overload mouse models. Our findings elucidate the specific pathways through which excess iron accelerates OA progression and highlights potential targets for therapeutic intervention aimed at modulating iron levels to mitigate OA symptoms. KEY MESSAGES: Iron overload alters joint iron metabolism, increasing OA markers in cartilage and synovium. High iron levels in mice accelerate OA, highlighting genetic and dietary impacts. Excess iron prompts chondrocyte iron storage response, signalling potential OA pathways. Iron dysregulation linked to increased cartilage degradation and synovial inflammation. Our findings support targeted therapies for OA based on iron modulation strategies.

Chronic rose oxide and exercise synergistically modulate cardiovascular and autonomic functions in hypertensive rats.

With the alarming rise in cases of arterial hypertension worldwide, there is an urgent need to develop combined therapies to mitigate this scenario. Rose oxide (RO), a monoterpene with anti-inflammatory and hypotensive properties, emerges as an alternative. The present study is the first to evaluate the effect of RO administered chronically and combined with physical exercise (swimming) since both have been reported to have beneficial impacts on hypertension. Male SHR and Wistar rats (aged 12weeks) received RO for 34 consecutive days (orally; 100mg/kg). The progression of systolic arterial pressure (SAP) was monitored through tail-cuff plethysmography. Twenty-four hours before the end of the treatment, the animals were anesthetized, and the femoral artery and vein were cannulated to record the pulsatile arterial pressure and to administer drugs, respectively. Hemodynamic and autonomic parameters and baroreflex sensitivity and intrinsic heart rate (IHR) were evaluated. Treatment with RO, administered alone or combined with exercise, reduced SAP and mean arterial pressure in SHR. The swimming protocol did not prevent increases in BP, but when combined with RO, it improved autonomic control, assessed through heart rate variability and parasympathetic tone. IHR was attenuated in SHR, and none of the treatments reversed this response. Therefore, combining RO with physical exercise may enhance their antihypertensive effects, improving autonomic function, reducing oxidative stress and inflammation, providing synergistic cardiovascular benefits, improving metabolic health, promoting a comprehensive lifestyle intervention, and potentially allowing for reduced medication dosages. This multifaceted approach could offer a more effective and sustainable strategy for managing hypertension.

Fracture morphology and ossification process of the keel bone in modern laying hens based on radiographic imaging.

Keel bone fractures (KBF) are one of the most important welfare problems in commercial laying hens. Despite extensive research on the matter, its etiology remains unclear. Studying fracture characteristics in radiographic images can aid in the understanding of the disorder. The aim of the current study was to provide detailed description of fracture characteristics and explore ossification in the keel bone. In this descriptive study, repeated cross-sectional sampling was performed in one commercial laying hen flock. The flock was visited at 11 time points from 17-57 weeks of age (WOA), radiographing 30 laying hens at each visit resulting in altogether 330 unique radiographs. Fracture characteristics and the keel bone's level of ossification were assessed in each radiograph. In total, 344 fractures were recorded, of which 71.5% were complete and 28.5% were incomplete. Of the complete fractures, 82.9% were recorded as transverse, and 15.9% as oblique. One comminuted and two butterfly fractures were recorded. The caudal third of the keel was the most common area for fractures. Fracture characteristics differed between the different regions of the keel bone; all incomplete fractures in the cranial third appeared on the ventral surface of the keel, whilst the majority of incomplete fractures on the caudal third appeared on the dorsal surface. This indicates that the underlying etiology might differ between the cranial and caudal part. Folding fractures were observed in 18.6% of all the fractures, and occurred in both cranial-, and caudal third of the keel, indicating possible underlying disorders of calcium metabolism. All hens at 32 WOA and older had a fully ossified keel, based on radiographic evaluation. Displacement and soft tissue swelling are common characteristics in fractures of traumatic origin. We found a high frequency of simple fractures, without these characteristics, indicating that non-traumatic causes may be of higher importance than conventional beliefs.

Insulin receptor signalling in PDGFRβ-expressing cells influences systemic metabolism and negatively impacts lipid storage

Pericytes are vascular mural cells that support the microvasculature; their dysfunction contributes to diabetic retinopathy and has been linked to obesity in humans. To explore the role of pericyte insulin signalling on systemic metabolism we utilised male mice from our previously described PIR−/− (PIRKO) mouse line which has insulin receptor (Insr) knockout in PDGFRβ-expressing cells. These animals exhibit systemic insulin resistance from as early as 8-weeks of age, despite no change in body weight or activity level, and show altered body composition and hepatosteatosis. When challenged with high fat diet, PIR−/− remain insulin resistant but are protected from weight gain with reduced adipose tissue expansion across all depots and altered adipose morphology. Exhibiting parallels with the metabolically-obese-normal-weight (MONW) human phenotype, the PIR−/− line underlines the importance of pericyte biology in the development of both diabetes and obesity and establishes the angiopoietin (Ang)/Tie signalling pathway as a focus for future research.