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The Cochrane Database of Systematic... Mar 2023Phototherapy is a widely accepted, effective first-line therapy for neonatal jaundice. It is traditionally used continuously but intermittent phototherapy has been... (Review)
Review
BACKGROUND
Phototherapy is a widely accepted, effective first-line therapy for neonatal jaundice. It is traditionally used continuously but intermittent phototherapy has been proposed as an equally effective alternative with practical advantages of improved maternal feeding and bonding. The effectiveness of intermittent phototherapy compared with continuous phototherapy is unknown.
OBJECTIVES
To assess the safety and effectiveness of intermittent phototherapy compared with continuous phototherapy.
SEARCH METHODS
Searches were conducted on 31 January 2022 in the following databases: CENTRAL via CRS Web, MEDLINE and Embase via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.
SELECTION CRITERIA
We included RCTs, cluster-RCTs and quasi-RCTs comparing intermittent phototherapy with continuous phototherapy in jaundiced infants (both term and preterm) up to the age of 30 days. We compared intermittent phototherapy with continuous phototherapy by any method and at any dose and duration as defined by the authors.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected trials, assessed trial quality and extracted data from included studies. We performed fixed-effect analyses and expressed treatment effects as mean difference (MD), risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs). Our primary outcomes of interest were rate of decline of serum bilirubin, and kernicterus. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
We included 12 RCTs (1600 infants) in the review. There is one ongoing study and four awaiting classification. There was little or no difference between intermittent phototherapy and continuous phototherapy with respect to rate of decline of bilirubin in jaundiced newborn infants (MD -0.09 micromol/L/hr, 95% CI -0.21 to 0.03; I² = 61%; 10 studies; 1225 infants; low-certainty evidence). One study involving 60 infants reported no incidence of bilirubin induced brain dysfunction (BIND). It is uncertain whether either intermittent or continuous phototherapy reduces BIND because the certainty of this evidence is very low. There was little or no difference in treatment failure (RD 0.03, 95% CI 0.08 to 0.15; RR 1.63, 95% CI 0.29 to 9.17; 1 study; 75 infants; very low-certainty evidence) or infant mortality (RD -0.01, 95% CI -0.03 to 0.01; RR 0.69, 95% CI 0.37 to 1.31 I² = 0%; 10 studies, 1470 infants; low-certainty evidence). AUTHORS' CONCLUSIONS: The available evidence detected little or no difference between intermittent and continuous phototherapy with respect to rate of decline of bilirubin. Continuous phototherapy appears to be more effective in preterm infants, however, the risks of continuous phototherapy and the potential benefits of a slightly lower bilirubin level are unknown. Intermittent phototherapy is associated with a decrease in the total number of hours of phototherapy exposure. There are theoretical benefits to intermittent regimens but there are important safety outcomes that were inadequately addressed. Large, well designed, prospective trials are needed in both preterm and term infants before it can be concluded that intermittent and continuous phototherapy regimens are equally effective.
Topics: Infant; Infant, Newborn; Humans; Jaundice, Neonatal; Phototherapy; Bilirubin; Family
PubMed: 36867730
DOI: 10.1002/14651858.CD008168.pub2 -
Bioorganic & Medicinal Chemistry Mar 2023A series of Icariside II (ICS II) derivatives were synthesized, and their structure-activity relationships (SARs) were studied in this paper. The in vitro antitumor...
A series of Icariside II (ICS II) derivatives were synthesized, and their structure-activity relationships (SARs) were studied in this paper. The in vitro antitumor activities towards human breast cancer cell lines (MCF-7) were evaluated by Cell Counting Kit-8 (CCK-8 kit). Preliminary results showed that, compared with ICS II, most of the derivatives displayed good micromole level activities. Among the series of derivatives, the S27, which totally acetylated hydroxyl of ICS II, possessed highest cytotoxicity, with IC values of 0.70 ± 0.08 μM. Furthermore, compound S27 showed better selectivity than ICS II for cancer cells over normal cells. Our findings indicate that compound S27 may be a promising anticancer lead candidate drug.
Topics: Humans; Female; Cell Proliferation; Structure-Activity Relationship; Flavonoids; Breast Neoplasms; Antineoplastic Agents; Drug Screening Assays, Antitumor; Molecular Structure; Cell Line, Tumor; Dose-Response Relationship, Drug
PubMed: 36753987
DOI: 10.1016/j.bmc.2023.117188 -
ESC Heart Failure Apr 2023Heart failure with reduced ejection fraction (HFrEF) is a disease with high mortality and morbidity. Recent positive inotropic drug developments focused on cardiac...
AIMS
Heart failure with reduced ejection fraction (HFrEF) is a disease with high mortality and morbidity. Recent positive inotropic drug developments focused on cardiac myofilaments, that is, direct activators of the myosin molecule and Ca sensitizers for patients with advanced HFrEF. Omecamtiv mecarbil (OM) is the first direct myosin activator with promising results in clinical studies. Here, we aimed to elucidate the cellular mechanisms of the positive inotropic effect of OM in a comparative in vitro investigation where Ca -sensitizing positive inotropic agents with distinct mechanisms of action [EMD 53998 (EMD), which also docks on the myosin molecule, and levosimendan (Levo), which binds to troponin C] were included.
METHODS
Enzymatically isolated canine cardiomyocytes with intact cell membranes were loaded with Fura-2AM, a Ca -sensitive, ratiometric, fluorescent dye. Changes in sarcomere length (SL) and intracellular Ca concentration were recorded in parallel at room temperature, whereas cardiomyocyte contractions were evoked by field stimulation at 0.1 Hz in the presence of different OM, EMD, or Levo concentrations.
RESULTS
SL was reduced by about 23% or 9% in the presence of 1 μM OM or 1 μM EMD in the absence of electrical stimulation, whereas 1 μM Levo had no effect on resting SL. Fractional sarcomere shortening was increased by 1 μM EMD or 1 μM Levo to about 152%, but only to about 128% in the presence of 0.03 μM OM. At higher OM concentrations, no significant increase in fractional sarcomere shortening could be recorded. Contraction durations largely increased, whereas the kinetics of contractions and relaxations decreased with increasing OM concentrations. One-micromole EMD or 1 μM Levo had no effects on contraction durations. One-micromole Levo, but not 1 μM EMD, accelerated the kinetics of cardiomyocyte contractions and relaxations. Ca transient amplitudes were unaffected by all treatments.
CONCLUSIONS
Our data revealed major distinctions between the cellular effects of myofilament targeted agents (OM, EMD, or Levo) depending on their target proteins and binding sites, although they were compatible with the involvement of Ca -sensitizing mechanisms for all three drugs. Significant part of the cardiotonic effect of OM relates to the prolongation of systolic contraction in combination with its Ca -sensitizing effect.
Topics: Animals; Dogs; Myocytes, Cardiac; Heart Failure; Stroke Volume; Simendan; Myosins
PubMed: 36722665
DOI: 10.1002/ehf2.14300 -
Bi-enzyme competition based on ZIF-67 co-immobilization for real-time monitoring of exocellular ATP.Mikrochimica Acta Jan 2023Monitoring exocellular adenosine-5'-triphosphate (ATP) is a demanding task but the biosensor development is limited by the low concentration and rapid degradation of...
Monitoring exocellular adenosine-5'-triphosphate (ATP) is a demanding task but the biosensor development is limited by the low concentration and rapid degradation of ATP. Herein, we developed a simple yet effective biosensor based on ZIF-67 loaded with bi-enzymes of glucose (GOx) and hexokinase (HEX) for effective detection of ATP. In the confined space of the porous matrix, the bi-enzymes competed for the glucose substrate in the presence of ATP, facilitating the biosensor to detect low ATP concentrations down to the micromole level (3.75 μM) at working potential of 0.55 V (vs. Ag/AgCl). Furthermore, ZIF-67 with cobalt served as a porous matrix to specifically adsorb ATP molecules, allowing it to differentiate isomers with sensitivity of 0.53 nA/μM, RSD of 5.4%, and recovery rate of 93.3%. We successfully applied the fabricated biosensor to measure ATP secreted from rat PC12 cells in the pericellular space thus realizing time-resolving measurement. This work paved the path for real-time monitoring of ATP released by cells, which will aid in understanding tumor cell glycolysis and immune responses.
Topics: Animals; Rats; Enzymes, Immobilized; Glucose Oxidase; Hexokinase; Adenosine Triphosphate; Glucose
PubMed: 36695915
DOI: 10.1007/s00604-023-05652-y -
Annals of Intensive Care Jan 2023The anatomic site for central venous catheter insertion influences the risk of central venous catheter-related intravascular complications. We developed and validated a...
Development and validation of a multivariable model predicting the required catheter dwell time among mechanically ventilated critically ill patients in three randomized trials.
BACKGROUND
The anatomic site for central venous catheter insertion influences the risk of central venous catheter-related intravascular complications. We developed and validated a predictive score of required catheter dwell time to identify critically ill patients at higher risk of intravascular complications.
METHODS
We retrospectively conducted a cohort study from three multicenter randomized controlled trials enrolling consecutive patients requiring central venous catheterization. The primary outcome was the required catheter dwell time, defined as the period between the first catheter insertion and removal of the last catheter for absence of utility. Predictors were identified in the training cohort (3SITES trial; 2336 patients) through multivariable analyses based on the subdistribution hazard function accounting for death as a competing event. Internal validation was performed in the training cohort by 500 bootstraps to derive the CVC-IN score from robust risk factors. External validation of the CVC-IN score were performed in the testing cohort (CLEAN, and DRESSING2; 2371 patients).
RESULTS
The analysis was restricted to patients requiring mechanical ventilation to comply with model assumptions. Immunosuppression (2 points), high creatinine > 100 micromol/L (2 points), use of vasopressor (1 point), obesity (1 point) and older age (40-59, 1 point; ≥ 60, 2 points) were independently associated with the required catheter dwell time. At day 28, area under the ROC curve for the CVC-IN score was 0.69, 95% confidence interval (CI) [0.66-0.72] in the training cohort and 0.64, 95% CI [0.61-0.66] in the testing cohort. Patients with a CVC-IN score ≥ 4 in the overall cohort had a median required catheter dwell time of 24 days (versus 11 days for CVC-IN score < 4 points). The positive predictive value of a CVC-IN score ≥ 4 was 76.9% for > 7 days required catheter dwell time in the testing cohort.
CONCLUSION
The CVC-IN score, which can be used for the first catheter, had a modest ability to discriminate required catheter dwell time. Nevertheless, preference of the subclavian site may contribute to limit the risk of intravascular complications, in particular among ventilated patients with high CVC-IN score. Trials Registration NCT01479153, NCT01629550, NCT01189682.
PubMed: 36645531
DOI: 10.1186/s13613-023-01099-9 -
Micromachines Dec 2022To verify the existence of plasma with the potential to kill tumor cells, this paper designed a novel helium (He) micro-plasma jet array device and detected the...
To verify the existence of plasma with the potential to kill tumor cells, this paper designed a novel helium (He) micro-plasma jet array device and detected the concentration of typical long-lived reactive oxygen and nitrogen species (RONS) with oxidative activity generated by it. The paper described a new He micro-plasma jet array device consisting of nine flexible quartz capillaries with an inner diameter of 75 μm arranged in a 3 × 3 array. Sterilized ultrapure water (up water) was first treated with the He micro-plasma jet array device to activate it to form enriched RONS micro-plasma-activated water (μ-PAW), and then μ-PAW was added to the cell culture medium (with cells) to observe the proliferation of human glioma cells. The concentration of long-lived RONS, such as nitrate (NO), was detected according to Beer-Lambert's law in combination with UV spectrophotometry as well as a color development method. The MTT Cell Proliferation and Cytotoxicity Assay Kit combined with the Hoechst Staining Kit were used to assess the proliferation status of the cells. The results showed that the range of RONS concentration variation could be controlled in the order of micromoles (µmol), while plasma-induced tumor cell death is apoptosis that does not affect the surrounding environment.
PubMed: 36557443
DOI: 10.3390/mi13122145 -
Cureus Dec 2022The bladder is both an intraperitoneal and extraperitoneal structure. Its anatomical position increases its risk of rupture. The resultant urine leak or extravasation...
The bladder is both an intraperitoneal and extraperitoneal structure. Its anatomical position increases its risk of rupture. The resultant urine leak or extravasation can be intraperitoneal, extraperitoneal, or even both-with the former leading to more sinister outcomes. Intraperitoneal bladder rupture can lead to urinary ascites which along with anuria and abdominal pain, can present with an apparent abrupt decline in renal function as the creatinine-rich products diffuse across the peritoneal membrane. Glomerular filtration rate, a measure of kidney function is related to the levels of serum creatinine. Clinicians can therefore misdiagnose their patient with acute kidney injury when the serum creatinine is elevated as a consequence of urine being present in the peritoneal space. This is a case report of a 62-year-old male with pseudo-renal failure following intraperitoneal bladder rupture after a fall face-forwards three hours previously. The fall was due to icy conditions outside and no preceding symptoms were reported. He presented to the Accident and Emergency department with abdominal pain and no other positive symptoms. The patient had a good World Health Organisation (WHO) performance status with a background of hypertension, diabetes, and hypercholesterolemia. The bedside examination of the patient revealed a distended, abdomen with peritonitis. There were no signs of urogenital trauma. Blood testing revealed a low estimated glomerular filtration rate (eGFR) and raised creatinine (eGFR of 7 millilitres/minute and creatinine of 658 micromoles/litre). Computerised tomography examination of the abdomen and pelvis (CTAP) revealed free fluid within the peritoneal cavity and an irregular bladder wall. A CT cystogram and consultation with urology led to the diagnosis of intraperitoneal bladder rupture. The patient's renal function from an initial set of blood tests was reduced. This was not a true impairment in renal function but rather a complication secondary to extravasation of urine in the intraperitoneal space, ie., pseudo renal failure. This supposed impairment in renal function had numerous implications. It affected the choice of antibiotics; amoxicillin and gentamicin were given at a reduced dose due to the patient's renal function and the patient was prepared for operation theatre. The patient's blood creatinine was falsely elevated at 658 micromoles/litre due to the diffusion of creatinine from the free urine in the peritoneal space into the blood. This painted a false image of renal failure and protracted the clinical decision-making process. Relatively simple measures like an ascitic tap could have helped to differentiate this from a true acute kidney injury and could have resulted in quicker and more effective treatment of this patient. The patient went on to have bladder repair under urology. His follow-up cystogram four weeks post-operation did not show any leak.
PubMed: 36514699
DOI: 10.7759/cureus.32360 -
Science Advances Dec 2022Photo- or electroreduction of carbon dioxide into highly valued products offers a promising strategy to achieve carbon neutrality. Here, a series of...
Photo- or electroreduction of carbon dioxide into highly valued products offers a promising strategy to achieve carbon neutrality. Here, a series of polyoxometalate-based metal-organic frameworks (M-POMOFs) were constructed by metalloporphyrins [tetrakis(4-carboxyphenyl)-porphyrin-M (M-TCPPs)] and reductive POM for photo- and electrocatalytic carbon dioxide reductions (PCR and ECR, respectively), and the mysteries between the roles of single metal site and cluster in catalysis were disclosed. Iron-POMOF exhibited an excellent selectivity (97.2%) with high methane production of 922 micromoles per gram in PCR, together with superior Faradaic efficiency for carbon dioxide to carbon monoxide (92.1%) in ECR. The underlying mechanisms were further clarified. Photogenerated electrons transferred from iron-TCPP to the POM cluster for methane generation under irradiation, while the abundant electrons flowed to the center of iron-TCPP for carbon monoxide formation under the applied electric field. The specific multielectron products generated on iron-POMOF through switching driving forces to control electron flow direction between single metal site and cluster catalysis.
PubMed: 36490347
DOI: 10.1126/sciadv.add5598 -
International Journal of Environmental... Nov 2022We investigated vanadium, i.e., a redox-active heavy metal widely known for the generation of oxidative stress in cultured mammalian cells, to determine its ability to...
We investigated vanadium, i.e., a redox-active heavy metal widely known for the generation of oxidative stress in cultured mammalian cells, to determine its ability to interfere with common oxidative stress-related bioassays in cell-free conditions. We first assessed the prooxidant abilities (HO level, oxidation of DHR 123, and DCFH-DA dyes) and antioxidant capacity (ABTS, RP, OH, and DPPH methods) of popular mammalian cell culture media, i.e., Minimal Essential Medium (MEM), Dulbecco's Minimal Essential Medium (DMEM), Dulbecco's Minimal Essential Medium-F12 (DMEM/F12), and RPMI 1640. Out of the four media studied, DMEM has the highest prooxidant and antioxidant properties, which is associated with the highest concentration of prooxidant and antioxidant nutrients in its formulation. The studied vanadium compounds, vanadyl sulphate (VOSO), or sodium metavanadate (NaVO) (100, 500, and 1000 µM), either slightly increased or decreased the level of HO in the studied culture media. However, these changes were in the range of a few micromoles, and they should rather not interfere with the cytotoxic effect of vanadium on cells. However, the tested vanadium compounds significantly stimulated the oxidation of DCFH-DA and DHR123 in a cell-independent manner. The type of the culture media and their pro-oxidant and antioxidant abilities did not affect the intensity of oxidation of these dyes by vanadium, whereas the vanadium compound type was important, as VOSO stimulated DCFH-DA and DHR oxidation much more potently than NaVO. Such interactions of vanadium with these probes may artefactually contribute to the oxidation of these dyes by reactive oxygen species induced by vanadium in cells.
Topics: Animals; Reactive Oxygen Species; Vanadium; Antioxidants; Hydrogen Peroxide; Artifacts; Vanadium Compounds; Culture Media; Coloring Agents; Mammals
PubMed: 36429933
DOI: 10.3390/ijerph192215214