scholarly journals Breed-related expression patterns of Ki67, γH2AX, and p21 during ageing in the canine liver

Author(s):  
Laura J. A. Hardwick ◽  
Andre J. Kortum ◽  
Fernando Constantino-Casas ◽  
Penny J. Watson

AbstractCellular senescence is a molecular hallmark of ageing that is associated with multiple pathologies, and DNA damage marker γH2AX, together with cell cycle inhibitor p21, have been used as senescence markers in multiple species including dogs. Idiopathic canine chronic hepatitis has recognised breed-related differences in predisposition and prognosis, but reasons behind this are poorly understood. This retrospective study using archived post mortem tissue aimed to provide insight into liver ageing in 51 microscopically normal canine livers across seven breed categories, including those with and without increased risk of chronic hepatitis. Immunohistochemistry was conducted for γH2AX, p21, and cell proliferation marker Ki67, and the mean number of positive hepatocytes per high power field was determined. All three markers were strongly correlated to each other, but no age-dependent expression was seen in the combined study population. Overall expression levels were low in most dogs, with median values representing less than 1.5% of hepatocytes, but this increased to 20–30% in individual dogs at the upper end of the range. Individual breed differences were noted in two breeds that have increased risk of chronic hepatitis, with English Springer Spaniels having lower expression of Ki67 than other dogs, and Labradors having higher expression of Ki67 and γH2AX than other dogs. These results warrant further investigation in these breeds and highlight a need to validate reliable markers of cellular senescence in dogs.

Crisis ◽  
2014 ◽  
Vol 35 (5) ◽  
pp. 330-337 ◽  
Author(s):  
Cun-Xian Jia ◽  
Lin-Lin Wang ◽  
Ai-Qiang Xu ◽  
Ai-Ying Dai ◽  
Ping Qin

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.


2020 ◽  
Vol 48 (4) ◽  
pp. 329-334
Author(s):  
Soo Jin Han ◽  
Seung Mi Lee ◽  
Sohee Oh ◽  
Subeen Hong ◽  
Jeong Won Oh ◽  
...  

AbstractBackgroundIn monochorionic twin pregnancy, placental anastomosis and inter-twin blood transfusion can result in specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). It is well established that adverse outcomes are increased in TTTS, but reports on the neonatal and long-term outcomes of TAPS are lacking. The objective of this study was to evaluate the neonatal and neurodevelopmental outcomes in spontaneous TAPS.MethodsThe study population consisted of monochorionic twin pregnancies with preterm birth (24–37 weeks of gestation) between November 2003 and December 2016 and in which cord blood was taken at the time of delivery. According to the result of hemoglobin in cord blood, the study population was divided into two groups: a spontaneous TAPS group and a control group. Neonatal and neurodevelopmental outcomes were compared between the two groups.ResultsDuring the study period, 11 cases were diagnosed as spontaneous TAPS (6.4%). The TAPS group had lower gestational age at delivery and had a higher risk for cesarean delivery. However, neonates with TAPS were not at an increased risk for neonatal mortality and significant neonatal morbidity. In addition, the frequency of severe cerebral lesion during the neonatal period and the risk of cerebral palsy at 2 years of age were not different between the two groups.ConclusionThe spontaneous TAPS diagnosed by postnatal diagnostic criteria was not associated with the increased risk of adverse neonatal and neurodevelopmental outcomes. Further studies are needed to evaluate the morbidity of antenatally diagnosed TAPS.


2021 ◽  
pp. 1-36
Author(s):  
Ahmed A. Alhassani ◽  
Frank B. Hu ◽  
Bernard A. Rosner ◽  
Fred K. Tabung ◽  
Walter C. Willett ◽  
...  

ABSTRACT The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food based, reduced rank regression (RRR) derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34,940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years, and dietary data through validated semi-quantitative food frequency questionnaires every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) to the lowest quintile was 0.99 (95% confidence interval: 0.89 -1.10, p-value for trend = 0.97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile to the lowest was 1.39 (95% confidence interval: 0.98 -1.96, p-value for trend = 0.03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated EDIP was significantly associated with increased risk of periodontitis only among nonsmokers who were obese. Hence, this association must be interpreted with caution.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hetti von Hellens ◽  
Leea Keski-Nisula ◽  
Heidi Sahlman

Abstract Background The maternal use of paracetamol during pregnancy has been associated with the development of preeclampsia. This study aims to clarify whether the connection is causal or whether it is due to reverse causation. Methods This study is a continuation of the retrospective case cohort study examining 2,508 pregnant women using a variety of drugs and the development of preeclampsia (1,252 women with preeclampsia and 1,256 controls). For the purposes of this study, more precise data was collected from several hospital databases of the women among this cohort who had reported taking paracetamol during pregnancy (indications, gestational period etc.); this was evaluated in association with the development of preeclampsia. Results 5.5% (100 cases and 37 controls) of all the study population (2,508) had clearly reported paracetamol use. Women with preeclampsia had used significantly more often paracetamol during pregnancy compared to controls (cases 8.0%, controls 2.9%, p < 0.001). The difference was most evident in the third trimester (after the 29th GW) and the use of paracetamol was associated with both mild and severe preeclampsia. Headache and “general pain” were the most common indications for medication among all paracetamol users. Conclusions The use of paracetamol in the third trimester of pregnancy was associated with preeclampsia. This observation indicates that association between paracetamol use and preeclampsia is probably due to reverse causation, i.e. women with preeclampsia experience more headaches due to preeclampsia symptoms since this association was not detected with the use of paracetamol in earlier stages of pregnancy.


Author(s):  
Maria Värendh ◽  
Christer Janson ◽  
Caroline Bengtsson ◽  
Johan Hellgren ◽  
Mathias Holm ◽  
...  

Abstract Purpose Humans have a preference for nasal breathing during sleep. This 10-year prospective study aimed to determine if nasal symptoms can predict snoring and also if snoring can predict development of nasal symptoms. The hypothesis proposed is that nasal symptoms affect the risk of snoring 10 years later, whereas snoring does not increase the risk of developing nasal symptoms. Methods In the cohort study, Respiratory Health in Northern Europe (RHINE), a random population from Denmark, Estonia, Iceland, Norway, and Sweden, born between 1945 and 1973, was investigated by postal questionnaires in 1999–2001 (RHINE II, baseline) and in 2010–2012 (RHINE III, follow-up). The study population consisted of the participants who had answered questions on nasal symptoms such as nasal obstruction, discharge, and sneezing, and also snoring both at baseline and at follow-up (n = 10,112). Results Nasal symptoms were frequent, reported by 48% of the entire population at baseline, with snoring reported by 24%. Nasal symptoms at baseline increased the risk of snoring at follow-up (adj. OR 1.38; 95% CI 1.22–1.58) after adjusting for age, sex, BMI change between baseline and follow-up, and smoking status. Snoring at baseline was associated with an increased risk of developing nasal symptoms at follow-up (adj. OR 1.22; 95% CI 1.02–1.47). Conclusion Nasal symptoms are independent risk factors for development of snoring 10 years later, and surprisingly, snoring is a risk factor for the development of nasal symptoms.


Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 210
Author(s):  
Martynas Ridziauskas ◽  
Birutė Zablockienė ◽  
Ligita Jančorienė ◽  
Artūras Samuilis ◽  
Rolandas Zablockis ◽  
...  

Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023–0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.


1995 ◽  
Vol 147 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
Randal D. Streck ◽  
Veeraramani S. Rajaratnam ◽  
Renata B. Fishman ◽  
Peggy J. Webb

ABSTRACT Matemal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.


2012 ◽  
Vol 6 ◽  
pp. CMPed.S9349
Author(s):  
J. Uberos ◽  
V. Fernéndez-Puentes ◽  
M. Molina-Oya ◽  
R. Rodrïguez-Belmonte ◽  
A. Ruïz-López ◽  
...  

Objectives The present study, which is part of the ISRCTN16968287 clinical assay, is aimed at determining the effects of cranberry syrup or trimethoprim treatment for UTI. Methods This Phase III randomised clinical trial was conducted at the San Cecilio Clinical Hospital (Granada, Spain) with a study population of 192 patients, aged between 1 month and 13 years. Criteria for inclusion were a background of recurrent UTI, associated or otherwise with vesico-ureteral reflux of any degree, or renal pelvic dilatation associated with urinary infection. Each child was randomly given 0.2 mL/Kg/day of either cranberry syrup or trimethoprim (8 mg/mL). The primary and secondary objectives, respectively, were to determine the risk of UTI and the levels of phenolic acids in urine associated with each intervention. Results With respect to UTI, the cranberry treatment was non-inferior to trimethoprim. Increased urinary excretion of ferulic acid was associated with a greater risk of UTI developing in infants aged under 1 year (RR 1.06; CI 95% 1.024–1.1; P = 0.001). Conclusions The results obtained show the excretion of ferulic acid is higher in infants aged under 1 year, giving rise to an increased risk of UTI, for both treatment options.


2016 ◽  
Vol 7 (6) ◽  
pp. 678-684 ◽  
Author(s):  
M. J. Davies ◽  
A. R. Rumbold ◽  
M. J. Whitrow ◽  
K. J. Willson ◽  
W. K. Scheil ◽  
...  

The study of very early pregnancy loss is impractical in the general population, but possible amongst infertility patients receiving carefully monitored treatments. We examined the association between fetal loss and the risk of birth defects in the surviving co-twin in a retrospective cohort study of infertility patients within an infertility clinic in South Australia from January 1986 to December 2002, linked to population registries for births, terminations and birth defects. The study population consisted of a total of 5683 births. Births from singleton pregnancies without loss were compared with survivors from (1) pregnancies with an empty fetal sac at 6–8 weeks after embryo transfer, (2) fetal loss subsequent to 8-week ultrasound and (3) multiple pregnancy continuing to birth. Odds ratios (OR) for birth defects were calculated with adjustment for confounders. Amongst infertility patients, the prevalence of birth defects was 7.9% for all twin pregnancies without fetal loss compared with 14.6% in pregnancies in which there had been an empty sac at ultrasound, and 11.6% for pregnancies with fetal loss after 6–8 weeks. Compared with singleton pregnancies without loss, the presence of an empty sac was associated with an increased risk of any defect (OR=1.90, 95% confidence intervals (CI)=1.09–3.30) and with multiple defects (OR=2.87, 95% CI=1.31–6.28). Twin pregnancies continuing to birth without loss were not associated with an overall increased prevalence of defects. We conclude that the observed loss of a co-twin by 6–8 weeks of pregnancy is related to the risk of major birth defects in the survivor.


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