Notes

Gender-focused education increases management regarding woman medical college students: A randomised trial.
Here, it is important to consider interactions with CYP3A4-effective drugs.In most cases, APL is treated "chemotherapy-free" with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). In high-risk patients, the combination of chemotherapy and ATRA is still standard.Moreover, maintenance therapies were (re)established as an important therapeutic element of post-remission therapy. For example, Midostaurin is used in patients with FLT3 mutations, as is the multikinase inhibitor sorafenib after allogeneic stem cell transplantation. In addition, oral azacitidine is available for non-allogeneic transplant eligible patients in first complete remission. These new drugs have improved prognosis and resulted in a more individualized therapy mostly driven by genetic aberrations. This development will continue in the next years and will significantly improve treatment options, especially for older patients.Helicobacter pylori (H. pylori) gastritis and non-steroidal anti-inflammatory drug (NSAID) intake are the most important risk factors for peptic ulcer disease (PUD) and ulcer bleeding. H. pylori infection was shown to increase the risk of ulcer bleeding in patients with PUD who are taking NSAID, aspirin, or another antiplatelet drug. H. pylori-positive patients on combined platelet aggregation inhibition are at the highest risk of bleeding. Evidence-based interdisciplinary treatment recommendations for the safe use of NSAID have been released. For patients with a moderate risk of PUD, the combination of NSAID and a proton pump inhibitor (PPI) or a monotherapy with a selective cyclooxygenase-2 (COX-2) inhibitor is recommended, whereas patients with a high risk of bleeding should receive a combination of a selective COX-2 inhibitor and a PPI. According to a recent randomized trial, hemodynamically stable patients with signs of upper gastrointestinal bleeding and an increased risk of death (Glasgow-Blatchford Score ≥ 12) undergoing endoscopy 6-24 after consultation do not have any disadvantage in terms of 30-day mortality compared to patients receiving endoscopy within 6 hours. After successful endoscopic hemostasis, additional prophylactic angiographic embolization does not reduce the risk of recurrent bleeding. Successful H. pylori eradication reduces the risk of developing gastric cancer (GC) in first-degree relatives of patients with GC by 73 %. In patients with successful endoscopic treatment of early GC, H. pylori testing with subsequent eradication also halves the rate of metachronous GC. Clarithromycin-based triple therapy for H. pylori eradication shows a decreasing effectiveness due to increasing antibiotic resistance, especially against macrolides. Accordingly, bismuth-containing quadruple therapy is widely recommended as the standard empiric first-line therapy.Dysnatremia is a common occurrence in patients with COVID-19 and is associated with higher mortality and risk for septic conditions. The pathomechanisms are probably multifaceted, but severe hyponatremia may also occur as a result of underlying SIADH or hypocortisolism. Patients with preexisting AVP dysfunction, like SIADH or diabetes insipidus, are at high risk for severe electrolyte imbalances in the event of a COVID-19 infection.The recently growing use of immune checkpoint inhibitors in oncology is associated with a spectrum of endocrine immune-related adverse events (endocrine irAEs). These AEs usually occur unpredictably and may even manifest after discontinuation of the anticancer therapy. Hyponatremia is a common factor of several endocrine irAEs and may serve as a red flag biomarker for possibly underlying endocrine irAEs such as hypophysitis or adrenalitis. New-onset hyponatremia should always prompt a comprehensive diagnostic workup and exclusion of endocrine irAEs before the diagnosis of SIADH is made.Hyponatremia with severe symptoms should be treated with hypertonic (3 %) saline solution to resolve the cerebral edema and prevent from detrimental neurological sequelae. Both rapid intermittent bolus (RIB) therapy and continuous infusion therapy have now been reported to be safe and equally effective. The RIB therapy limits the risk of overcorrection and requires less often re-lowering treatment than continuous infusion therapy.Fluid restriction has long been considered as first-line treatment of chronic hyponatremia due to SIADH. Additional treatment with Furosemid and/or oral NaCl tablets does not improve efficacy but reduces tolerance to therapy.Copeptin-based dynamic tests show higher diagnostic accuracy in the differential diagnosis of patients with hypotonic polyuria polydipsia syndrome than the indirect water deprivation test.A large proportion of patients with peripheral arterial disease (PAD) remain asymptomatic with respect to peripheral reduced perfusion. Most symptomatic patients present with walking distance limitation, intermittent claudication. In the advanced stage, critical limb ischemia, rest pain, gangrene, or ulceration occur.Treatment goals for patients with PAD differ depending on the stage of symptoms. In patients with intermittent claudication, the focus is on symptom relief with improvement in pain-free and maximal walking distance. In patients with critical limb ischemia, the focus is on leg preservation, improvement of quality of life, and amputation-free survival.Regardless of the stage of symptoms, cardiovascular risk factors should be optimally adjusted to reduce peripheral vascular, cardiovascular, and cerebrovascular events.In addition to conservative therapy with intensive gait training, endovascular and open vascular surgical revascularization are significant in the treatment of PAD.
OFA hr/hr rats have deficient lactation with impaired suckling-induced PRL release. Unlike their background strain, Sprague-Dawley (SD) rats, OFA rats display abnormal mediobasal hypothalamus (MBH) dopaminergic tone during late pregnant and lactation. We explored if the expression of MBH components, including various receptors (R) and proteins that regulate the dopaminergic system is altered in mid-lactating OFA compared to SD rats, which may be associated to the abnormality.

Four groups of mid-lactating rats were used continuous lactation; pups separated overnight; 30 min suckling (S); 2h or 4h S after separation. Mothers were sacrificed to obtain serum for PRL RIA and MBHs to determine tyrosine hydroxylase (TH), PRL-R, PRL signaling molecules (activator STAT5b; inhibitors SOCS1, SOCS3, CIS), opioids (PENK, PDYN) and µ- and κ-opioid R (MOR, KOR) mRNA expression by qPCR and phospho-TH (p-TH) and TH proteins by Western blot.

suckling-induced PRL was lower in OFA and p-TH expression diminished in both strains. Separation increased TH mRNA and protein in SD, which decreased after 4h S, but OFA protein levels remained unchanged. Separation of pups resulted in decreased PRL-R and CIS expression in SD but increased PRL-R and SOCS3 in OFA. Despite the lower PRL-R, STAT5b, SOCS1 and SOCS3 levels in OFA compared to SD, suckling diminished them further. We observed subtle changes in SD opioids and their R, but in OFA, suckling decreased PENK, KOR and MOR.

different patterns of TH, opioids, their R, and PRL signaling inhibitors expression with conserved TH activation by suckling may disturb the balance between stimulation and inhibition of PRL release resulting in impaired suckling-induced PRL secretion in OFA rats.
different patterns of TH, opioids, their R, and PRL signaling inhibitors expression with conserved TH activation by suckling may disturb the balance between stimulation and inhibition of PRL release resulting in impaired suckling-induced PRL secretion in OFA rats.
Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most prevalent complications of cardiac surgery, while the renal and overall prognoses of chronic kidney disease (CKD) patients with CSA-AKI are extremely poor. However, there is little published information on the occurrence of CSA-AKI in patients with CKD. The purpose of this study was to investigate the risk factors and prognostic factors of cardiac surgery-related AKI in patients with CKD.

A retrospective study was performed on CKD patients who underwent cardiac surgery at a tertiary referral teaching hospital. CSA-AKI was defined based on the KDIGO criteria. The risk factors for CSA-AKI and the factors affecting renal function recovery at discharge or death in patients with AKI were investigated.

Among 1638 CKD patients enrolled, the incidence of CSA-AKI was 50.55%. AKI patients' in-hospital mortality was higher than patients without AKI (AKI vs. no AKI, 4.7 vs. 0.9%, p < 0.001). Multivariate logistic regression analysis showmodifiable factors may help improve the prognosis of patients with CKD.The presence of mesenchymal progenitor cells (MPCs) in rheumatoid arthritis (RA) articular cartilage is sparsely investigated largely owing to the persistent pathogenic disease condition and lack of specific biomarkers. Considering the recent advancements for potential cell-based therapies in immunomodulatory diseases, such as RA, this in vitro study was aimed at investigating the cellular, molecular and differentiation characteristics of human RA cartilage-derived MPCs. Articular cartilage fragments from RA patients were obtained for the isolation and characterization of MPCs on their cellular and biological properties, cytogenic stability, pluripotency, and plasticity. Established MPCs were phenotypically identified using a panel of markers and their differentiation ability into mesenchymal lineages was assessed by cytochemical staining and the expression of molecular markers. MPCs displayed a heterogeneous population of cells with characteristic features of multipotent stem cells. Cells had higher viability, proliferative rate and colony-forming ability. Further, MPCs showed the expression of pluripotency markers, cytogenetic stability and minimal replicative senescence. In addition, MPCs differentiated into osteocytes, adipocytes and chondrocytes, and modulated the expression of each lineage-specific gene markers. The results demonstrated the availability of a viable pool of MPCs residing in RA cartilage, which could serve as an ideal cell source for reinstating native homotypic cartilage.
Fat mass and obesity-associated (FTO) gene is strongly associated with obesity which brings a major health threat. Altered expression of its encoded protein FTO in the hypothalamus has been identified to contribute to central control of appetite and body weight. However, its molecular mechanisms remain elusive.

Mouse hypothalamic POMC cell line N43/5 was treated with FTO inhibitor rhein, FTO shRNA, or extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 to inhibit FTO or ERK1/2. Thiamet G OGA inhibitor Rhein and U0126 were injected into lateral ventricle of the mice by intracerebroventricular cannulation. Western blotting and immunofluorescent assays were performed to monitor protein level.

This study identified that inhibition of FTO in N43/5 cells led to phosphorylation of signal transducer and activator of transcription 3 (STAT3) at S727 site and induced p-STAT3-S727 nuclear translocation. We further showed that FTO inhibition promoted phosphorylation of ERK1/2; specific inhibition of ERK1/2 signaling by U0126 could abolish the effect of FTO inhibition on STAT3-S727 phosphorylation and nuclear translocation.
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