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5 days compared to 0.9 days using existing statistical methods. This pattern holds over the range of study temperatures included in the dataset. Increasing temperature from 21°C to 34°C decreased the EIP50 from 16.1 to 8.8 days. Our work highlights the importance of mechanistic modelling of sporogony to (1) improve estimates of malaria transmission under different environmental conditions or disease control programs and (2) evaluate novel interventions that target the mosquito life stages of the parasite.Short QT (SQT) syndrome is a genetic cardiac disorder characterized by an abbreviated QT interval of the patient's electrocardiogram. The syndrome is associated with increased risk of arrhythmia and sudden cardiac death and can arise from a number of ion channel mutations. Cardiomyocytes derived from induced pluripotent stem cells generated from SQT patients (SQT hiPSC-CMs) provide promising platforms for testing pharmacological treatments directly in human cardiac cells exhibiting mutations specific for the syndrome. However, a difficulty is posed by the relative immaturity of hiPSC-CMs, with the possibility that drug effects observed in SQT hiPSC-CMs could be very different from the corresponding drug effect in vivo. In this paper, we apply a multistep computational procedure for translating measured drug effects from these cells to human QT response. This process first detects drug effects on individual ion channels based on measurements of SQT hiPSC-CMs and then uses these results to estimate the drug effects on ventricular action potentials and QT intervals of adult SQT patients. We find that the procedure is able to identify IC50 values in line with measured values for the four drugs quinidine, ivabradine, ajmaline and mexiletine. In addition, the predicted effect of quinidine on the adult QT interval is in good agreement with measured effects of quinidine for adult patients. Consequently, the computational procedure appears to be a useful tool for helping predicting adult drug responses from pure in vitro measurements of patient derived cell lines.
Neonatal jaundice is a frequent benign condition in newborns. However, a rapid diagnosis must be established for its most appropriate treatment. The objective of this study was to measure the correlation between total serum bilirubin (TSB) and transcutaneous bilirubin (in forehead and sternum) in full-term newborns at 3400 m above sea level.
We conducted a prospective and cross-sectional study in full-term newborns with clinical jaundice from the Hospital Regional in Cusco-Peru. General characteristics and measurement of TSB, transcutaneous forehead bilirubin (TcBF), and transcutaneous bilirubin in the sternum (TcBS) were explored. Correlation, sensitivity, and specificity were calculated. Receiver operating characteristic (ROC) curves were constructed using the SPSS statistical package, version 22.0.
A total of 123 newborns were evaluated. The mean bilirubin values were 13.7 ± 3.5 for TcBF, 14.1 ± 3.1 for TcBS, and 13.8 ± 3.9 for TSB. In addition, Pearson correlation coefficients between TSB/TcBF and TSB/TcBS were 0.90 and 0.91, respectively (p < 0.001). For the percentile 95 cut-off point, a sensitivity of 93% and 100% and a specificity of 89% and 80% were obtained for TcBF and TcBS, respectively, with an area under the curve of 0.813 for TcBF and 0.815 for TcBS (p < 0.001).
Measurement of transcutaneous bilirubin is a fast and painless method that can be considered a reliable tool for screening and monitoring neonatal jaundice, but not for a definitive diagnosis to decide the use of phototherapy in full-term newborns at 3400 m above sea level.
Measurement of transcutaneous bilirubin is a fast and painless method that can be considered a reliable tool for screening and monitoring neonatal jaundice, but not for a definitive diagnosis to decide the use of phototherapy in full-term newborns at 3400 m above sea level.BACKGROUND Clozapine is a well-proven atypical antipsychotic drug used for therapy of treatment-resistant schizophrenia. Over the last decades only a few cases of clozapine poisoning have been reported. Hence, guidelines for in-hospital management are currently not available. Most of the reported cases underwent detoxication measures as charcoal therapy and/or gastric lavage. However, there is no evidence for primary detoxication to improve clinical outcome. VT103 mw In contrast, use of therapy with intravenous physostigmine in the case of anticholinergic syndrome is restricted due to concerns about safety and dosing. We present a case of acute high-dose clozapine poisoning without detoxication and complete recovery supported by physostigmine. CASE REPORT We report the case of a 28-year-old man with prior diagnosed schizophrenia who presumably ingested 8 g (regular maximum daily dose 900 mg/d) of clozapine with uncertain intent. Initial computed tomography (CT) showed pulmonary infiltrates and widespread pneumomediastinum and soft-tissue emphysema of unknown genesis. The patient developed a progressive impairment of vigilance and respiratory insufficiency requiring invasive artificial ventilation for 31 h. Afterwards, an anticholinergic syndrome led again to impaired vigilance, tachycardia, and hyperventilation. To avoid risks associated with artificial ventilation, we applied physostigmine. Subsequently, the anticholinergic syndrome and the pneumomediastinum completely regressed and no further artificial ventilation was needed. CONCLUSIONS Based on the presumably ingested dosage, we present the likely highest reported nonfatal overdose of clozapine without detoxication. Additionally, we observed widespread pneumomediastinum as an uncommon complication. Our approach was to refrain from detoxication to minimize complications and to treat early with physostigmine because of anticholinergic syndrome to minimize its impact and to avoid artificial ventilation due do vigilance impairment.BACKGROUND The aims of this study included 3 aspects 1) assessing the expression of Apolipoprotein C1 (APOC1) in clear cell renal cell carcinoma (ccRCC) and normal groups; 2) evaluating the prognostic significance of APOC1 expression in the overall survival (OS) of ccRCC patients; and 3) exploring APOC1-related signaling pathways. MATERIAL AND METHODS The APOC1 expression value and clinical data of ccRCC patients were obtained from the cBioPortal database. We then evaluated the association of APOC1 expression with clinical characteristics of ccRCC patients. We also assessed the correlation between APOC1 expression and clinical outcome using Kaplan-Meier method. Our work then verified the independent prognostic factors of ccRCC by Cox regression analysis. Finally, the potential role of genes co-expressed with APOC1 was revealed via functional enrichment analysis. RESULTS Bioinformatic data revealed that APOC1 was expressed at higher levels in ccRCC tissue than in the normal group (all P less then 0.05). The high expression of APOC1 was associated with unfavorable prognosis of female patients (P less then 0.