Interleukin-6 bedside test in detecting chorioamnionitis in women with preterm premature rupture of fetal membranes

Objectives: About 30–80% of preterm deliveries following preterm premature rupture of fetal membranes (PPROM) are complicated by histological chorioamnionitis. To evaluate the accuracy of Interleukin-6 (IL-6) bedside test in detecting chorioamnionitis in women with PPROM.Material and methods: One hundred and ten (110) pregnant women with PPROM > 24 and < 34 weeks’ gestation, admitted for conservative management were included in this study. Participants were examined on admission using sterile speculum examination for assessment of IL-6 in the cervico-vaginal secretions using the IL-6 bedside test. The IL-6 bedside test was repeated for all participants once termination of pregnancy (TOP) decided. After TOP, placenta, umbilical cord, and fetal membranes samples were examined for histologic detection of chorioamnionitis (gold standard). The histological results were compared with IL-6 bedside test results to evaluate the accuracy of IL-6 bedside test in detecting chorioamnionitis in women with PPROM.Results: The IL-6 bedside test had 98.6% sensitivity, 94.7% specificity, 97.3% positive predictive value (PPV), 97.3% negative predictive value (NPV) and 97.3% overall accuracy in detecting chorioamnionitis. The sensitivity, specificity, NPV and overall accuracy of IL-6 bedside test (98.6%, 94.7%, 97.3%, and 97.3%; respectively) were significantly higher than the clinical and laboratory parameters of chorioamnionitis (65.3%, 57.9%, 46.8%, and 62.7%; respectively) (p = 0.04, 0.02, 0.001 and 0.03; respectively).Conclusions: The IL-6 bedside test is an accurate, non-invasive bedside test with 98.6% sensitivity, 94.7% specificity, 97.3% PPV, 97.3% NPV, and 97.3% overall accuracy in detecting chorioamnionitis. The IL-6 bedside test had significantly higher sensitivity, specificity, NPV, and overall accuracy than the clinical and laboratory parameters of chorioamnionitis

Optimization of the force characteristic of rotary motion type of electromagnetic actuator based on finite element analysis

The needs for non-invasive technique in breast cancer detection could enhance and preserve the future of medical field in Malaysia as well as countries around the world. Breast cancer has become the main concern nowadays not only for women but for man as well. In overall, the risk of women getting breast cancer is higher than man due to the denser tissue of breast in women compare to man. Beside the unawareness for the disease, the reason which contributes to this increasing number of breast cancer reported is also due to the limitations arising from modalities such as MRI, Mammography, ultrasound and other modalities. An alternative to current technologies should be improved for early detection and treatment which causes no physical harm to patients if possible. Thus, non-invasive and better technology in detecting breast cancer is very much needed in the current market. This paper will be discussing the insights of Magnetic Induction Tomography techniques in breast cancer detection

Mir142 loss unlocks IDH2R140-dependent leukemogenesis through antagonistic regulation of HOX genes

AML is a genetically heterogeneous disease and understanding how different co-occurring mutations cooperate to drive leukemogenesis will be crucial for improving diagnostic and therapeutic options for patients. MIR142 mutations have been recurrently detected in IDH-mutated AML samples. Here, we have used a mouse model to investigate the interaction between these two mutations and demonstrate a striking synergy between Mir142 loss-of-function and IDH2R140Q, with only recipients of double mutant cells succumbing to leukemia. Transcriptomic analysis of the non-leukemic single and leukemic double mutant progenitors, isolated from these mice, suggested a novel mechanism of cooperation whereby Mir142 loss-of-function counteracts aberrant silencing of Hoxa cluster genes by IDH2R140Q. Our analysis suggests that IDH2R140Q is an incoherent oncogene, with both positive and negative impacts on leukemogenesis, which requires the action of cooperating mutations to alleviate repression of Hoxa genes in order to advance to leukemia. This model, therefore, provides a compelling rationale for understanding how different mutations cooperate to drive leukemogenesis and the context-dependent effects of oncogenic mutations

An In-Depth Examination of the Natural Radiation and Radioactive Dangers Associated with Regularly Used Medicinal Herbs

The specific activity of U-238 and Th-232, as well as K-40 radionuclides, in twenty-nine investigated medicinal herbs used in Egypt has been measured using a high-purity germanium (HP Ge) detector. The measured values ranged from the BDL to 20.71 ± 1.52 with a mean of 7.25 ± 0.54 (Bq kg−1) for uranium-238, from the BDL to 29.35 ± 1.33 with a mean of 7.78 ± 0.633 (Bq kg−1) for thorium-232, and from 172 ± 5.85 to 1181.2 ± 25.5 with a mean of 471.4 ± 11.33 (Bq kg−1) for potassium-40. Individual herbs with the highest activity levels were found to be 20.71 ± 1.52 (Bq kg−1) for uranium-238 (H4, Thyme herb), 29.35 ± 1.33 (Bq kg−1) for thorium-232 (H20, Cinnamon), and 1181.2 ± 25.5 (Bq kg−1) for potassium-40 (H24, Worm-wood). (AACED) Ingestion-related effective doses over the course of a year of uranium-238 and thorium-232, as well as potassium-40 estimated from measured activity concentrations, are 0.002304 ± 0.00009 (minimum), 0.50869 ± 0.0002 (maximum), and 0.0373 ± 0.0004 (average)(mSv/yr). Radium equivalent activity (Raeq), annual gonadal dose equivalent (AGDE), absorbed gamma dose rate (Doutdoor, Dindoor), gamma representative level index (I), annual effective dose (AEDtotal), external and internal hazard index (Hex, Hin), and excess lifetime cancer risk were determined in medicinal plants (ELCR). The radiological hazards assessment revealed that the investigated plant species have natural radioactivity levels that are well within the internationally recommended limit. This is the first time that the natural radioactivity of therapeutic plants has been measured in Egypt. In addition, no artificial radionuclide (for example, 137Cs) was discovered in any of the samples. Therefore, the current findings are intended to serve as the foundation for establishing a standard safety and guideline for using these therapeutic plants in Egypt. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.PNURSP2022R173This work was funded by Princess Nourah bint, Abdulrahman University, Research Supporting Project number (PNURSP2022R173) Princess Nourah bint, Abdulrahman University, Riyadh, Saudi Arabia

Anti-tumour activity of a first-in-class agent NUC-1031 in patients with advanced cancer: results of a phase I study

Background Gemcitabine is used to treat a wide range of tumours, but its efficacy is limited by cancer cell resistance mechanisms. NUC-1031, a phosphoramidate modification of gemcitabine, is the first anti-cancer ProTide to enter the clinic and is designed to overcome these key resistance mechanisms. Methods Sixty-eight patients with advanced solid tumours who had relapsed after treatment with standard therapy were recruited to a dose escalation study to determine the recommended Phase II dose (RP2D) and assess the safety of NUC-1031. Pharmacokinetics and anti-tumour activity was also assessed. Results Sixty-eight patients received treatment, 50% of whom had prior exposure to gemcitabine. NUC-1031 was well tolerated with the most common Grade 3/4 adverse events of neutropaenia, lymphopaenia and fatigue occurring in 13 patients each (19%). In 49 response-evaluable patients, 5 (10%) achieved a partial response and 33 (67%) had stable disease, resulting in a 78% disease control rate. Cmax levels of the active intracellular metabolite, dFdCTP, were 217-times greater than those reported for equimolar doses of gemcitabine, with minimal toxic metabolite accumulation. The RP2D was determined as 825 mg/m2 on days 1, 8 and 15 of a 28-day cycle. Conclusions NUC-1031 was well tolerated and demonstrated clinically significant anti-tumour activity, even in patients with prior gemcitabine exposure and in cancers not traditionally perceived as gemcitabine-responsive

A state-of-the-art review of curve squeal noise: Phenomena, mechanisms, modelling and mitigation

[EN] Curve squeal is an intense tonal noise occurring when a rail vehicle negotiates a sharp curve. The phenomenon can be considered to be chaotic, with a widely differing likelihood of occurrence on different days or even times of day. The term curve squeal may include several different phenomena with a wide range of dominant frequencies and potentially different excitation mechanisms. This review addresses the different squeal phenomena and the approaches used to model squeal noise; both time-domain and frequency-domain approaches are discussed and compared. Supporting measurements using test rigs and field tests are also summarised. A particular aspect that is addressed is the excitation mechanism. Two mechanisms have mainly been considered in previous publications. In many early papers the squeal was supposed to be generated by the so-called falling friction characteristic in which the friction coefficient reduces with increasing sliding velocity. 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Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030