Site-characteristic expression and induction of trefoil factor family 1, 2 and 3 and malignant brain tumor-1 in normal and diseased intrahepatic bile ducts relates to biliary pathophysiology.

BACKGROUND/AIM: Trefoil factor family (TFF)1,2,3 are involved in a homeostasis/repair process of mucosal epithelia. In this study, the significance of TFF family and deleted in the malignant brain tumor-1 (DMBT1), a putative receptor of TFF2, in the intrahepatic biliary tree was investigated in normal and diseased livers. MATERIALS AND METHODS: Expression of TFF1,2,3 and DMBT1 were examined immunohistochemically in primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), chronic viral hepatitis (CVH), extrahepatic biliary obstruction (EBO), and normal livers. RESULTS: In normal livers, TFF1,3 and DMBT1 were infrequently detectable in large and rarely in small bile ducts, respectively. TFF2 was not detectable in large bile ducts. In large bile duct diseases (PSC and EBO), expression of TFF3 and DMBT1 were increased. In small bile duct diseases (PBC and CVH), expression of TFF2/DMBT1 was induced in moderately to severely damaged ducts irrespective of etiology. CONCLUSION: The intrahepatic biliary tree shows a site-characteristic expression and induction of TFF1,2,3 and DMBT1. In large bile ducts, TFF1,3 were constitutively expressed and increased in pathologic bile ducts. In small bile ducts, TFF2/DMBT1 is induced in damaged ducts irrespective of etiologies. However, the cytoprotective/repair property of TFF2/DMBT1 may not be enough to prevent the following bile duct loss in PBC.     

Rapid assessment of blood pressure in the obstetric day unit using Microlife MaM technology.

OBJECTIVE: To compare MaM technology with current methods of assessing blood pressure (BP) over time on the obstetric day unit. BACKGROUND: It is recommended that the average of repeated measures is used to confirm hypertension in pregnancy. The Microlife 3AC1 is a validated oscillometric device featuring "MaM" mode using the average of at least 3 BP readings 15 seconds apart. This allows rapid assessment of BP. The difference between each measurement is calculated and influences the percentage contribution to the final average reading. We compared MaM with readings taken in a conventional manner. METHODS: Blood pressure was measured in 30 hypertensive pregnant patients recruited from the obstetric day unit of a large teaching hospital. Single BP measurements were taken at 0, 15, 30, 60, and 90 minutes using the Microlife BP 3BT0-A[2]. Simultaneous measurements (in the opposite arm) were also taken at 0 and 90 minutes using MaM technology. RESULTS: Systolic BP fell over 90 minutes (p = 0.035) compared with the first single reading, but diastolic BP did not (p = 0.54). The difference between the first MaM and the first single reading was significantly different for systolic BP (5.6 mm Hg, p = 0.017), but not for diastolic (0.6 mm Hg, p = 0.39). The mean of all single readings and the first MaM reading were similar for both systolic and diastolic BP (SBP:0.3 mm Hg, p = 0.75, DBP: 0.2 mm Hg, p = 0.87). Conclusions: White-coat hypertension exists for systolic BP in the obstetric day unit. The MaM technology allows rapid and accurate characterization of blood pressure equivalent to repeated measures over 90 minutes.     

Help-seeking behaviour in primary care of men and women with a history of abuse: A Dutch cohort study

BackgroundPrevious studies show an association between a history of abuse and higher care demand. However, studies in general practice regarding help-seeking behaviour by patients (mainly male patients) with a history of abuse are scarce.ObjectivesTo analyse help-seeking behaviour in general practice of men and women with a history of abuse.MethodsA cohort study using data from a Dutch primary care registration network from 2015 to 2019. We included all patients aged ≥ 18 years who indicated on a questionnaire that they did or did not have a history of abuse. We analysed differences in contact frequency, types of contact, reason for encounter and diagnoses between men and women with or without a history of abuse.ResultsThe questionnaire had a response rate of 59% and resulted in 11,140 patients, of which 1271 indicated a history of abuse. Men and women with a history of abuse contact the general practitioner (GP) 1.5 times (95% CI 1.42–1.60) more often than men and women without a history of abuse, especially for psychological (rate ratio 1.97, 95% CI 1.79–2.17) and social (rate ratio 1.93, 95% CI 1.68–2.22) problems. Moreover, when diagnosed with a psychological or social problem, patients with a history of abuse contact the GP twice more often for these problems.ConclusionCompared to men and women without a history of abuse, men and women with a history of abuse visit their GP more often, particularly for psychological and social problems.     

Temporal integration as “common currency” of brain and self‐scale‐free activity in resting‐state EEG correlates with temporal delay effects on self‐relatedness

The self is a multifaceted phenomenon that integrates information and experience across multiple time scales. How temporal integration on the psychological level of the self is related to temporal integration on the neuronal level remains unclear. To investigate temporal integration on the psychological level, we modified a well‐established self‐matching paradigm by inserting temporal delays. On the neuronal level, we indexed temporal integration in resting‐state EEG by two related measures of scale‐free dynamics, the power law exponent and autocorrelation window. We hypothesized that the previously established self‐prioritization effect, measured as decreased response times or increased accuracy for self‐related stimuli, would change with the insertion of different temporal delays between the paired stimuli, and that these changes would be related to temporal integration on the neuronal level. We found a significant self‐prioritization effect on accuracy in all conditions with delays, indicating stronger temporal integration of self‐related stimuli. Further, we observed a relationship between temporal integration on psychological and neuronal levels: higher degrees of neuronal integration, that is, higher power‐law exponent and longer autocorrelation window, during resting‐state EEG were related to a stronger increase in the self‐prioritization effect across longer temporal delays. We conclude that temporal integration on the neuronal level serves as a template for temporal integration of the self on the psychological level. Temporal integration can thus be conceived as the “common currency” of neuronal and psychological levels of self.     

Changes in DNA Damage Repair Gene Expression and Cell Cycle Gene Expression Do Not Explain Radioresistance in Tamoxifen-Resistant Breast Cancer

Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that DNA damage repair or cell cycle genes are involved, and could therefore be targeted to preclude the occurrence of cross-resistance. We aimed to characterize the observed cross-resistance by investigating gene expression of DNA damage repair genes and cell cycle genes in estrogen receptor-positive MCF-7 breast cancer cells that were cultured to tamoxifen resistance. RNA sequencing was performed, and expression of genes characteristic for several DNA damage repair pathways was investigated, as well as expression of genes involved in different phases of the cell cycle. The association of differentially expressed genes with outcome after radiotherapy was assessed in silico in a large breast cancer cohort. None of the DNA damage repair pathways showed differential gene expression in tamoxifen-resistant cells compared to wild-type cells. Two DNA damage repair genes were more than two times upregulated (NEIL1 and EME2), and three DNA damage repair genes were more than two times downregulated (PCNA, BRIP1, and BARD1). However, these were not associated with outcome after radiotherapy in the TCGA breast cancer cohort. Genes involved in G₁, G₁/S, G₂, and G₂/M phases were lower expressed in tamoxifen-resistant cells compared to wild-type cells. Individual genes that were more than two times upregulated (MAPK13) or downregulated (E2F2, CKS2, GINS2, PCNA, MCM5, and EIF5A2) were not associated with response to radiotherapy in the patient cohort investigated. We assessed the expression of DNA damage repair genes and cell cycle genes in tamoxifen-resistant breast cancer cells. Though several genes in both pathways were differentially expressed, these could not explain the cross-resistance for irradiation in these cells, since no association to response to radiotherapy in the TCGA breast cancer cohort was found.     

Soluble Flt-1 as a diagnostic marker of pre-eclampsia

BACKGROUND: Serum levels of soluble fms-like tyrosine kinase (sFlt-1) increase in pre-eclampsia (PE). Aims: To determine whether concentrations of serum sFlt-1 can differentiate PE or superimposed PE (SPE) from gestational hypertension (GH) or chronic hypertension (CH). METHODS: Blood was collected from pregnant women being investigated for hypertension (blood pressure of > 140 and/or 90 mmHg). Normotensive (NP) and pre-eclamptic (PE-C) control ranges were measured. RESULTS: Patients with evolving hypertension in pregnancy eventually fell into four groups: GH (n = 14), PE (n = 7), CH (n = 9) and SPE (n = 9). Patients who later developed pre-eclampsia had a higher sFlt-1 (PE: 2.61 ng/mL and SPE: 2.77 ng/mL, respectively) than GH (P < 0.001) or CH (1.05 ng/mL, P = 0.11). Women with established PE at recruitment (PE-C; (n = 18) (3.13 ng/mL; interquartile range (IQR): 2.14-4.17 ng/mL) had a median sFlt-1 higher than NP (n = 18) (0.47 ng/mL; IQR: 0.11-0.89) (P < 0.0008). Patients with GH compared to NP had a slight increase (1.33 ng/mL, P < 0.003). Using a sFlt-1 cut-off of > or = 1.9 ng/mL yielded a sensitivity of 94% (95% confidence interval (CI) 73-100%) and specificity of 78% (95% CI 64-82%). CONCLUSIONS: sFlt-1 was elevated in women with PE compared to NP. The sFlt-1 also differentiated women destined to develop PE among those who presented with a diagnostic rise in maternal blood pressure. The sFlt-1 test is a useful diagnostic test for PE.