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Diagnostics (Basel, Switzerland) Jun 2024Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms presenting unique challenges in diagnosis and management. Traditional markers such as chromogranin... (Review)
Review
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms presenting unique challenges in diagnosis and management. Traditional markers such as chromogranin A (CgA), pancreatic polypeptide (PP), and neuron-specific enolase (NSE) have limitations in terms of specificity and sensitivity. Specific circulating markers such as serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and various gastrointestinal hormones such as gastrin, glucagon, somatostatin, and vasoactive intestinal peptide (VIP) have a role in identifying functional NENs. Recent advances in molecular and biochemical markers, also accounting for novel genomic and proteomic markers, have significantly improved the landscape for the diagnosis and monitoring of NENs. This review discusses these developments, focusing on both traditional markers such as CgA and NSE, as well as specific hormones like gastrin, insulin, somatostatin, glucagon, and VIP. Additionally, it covers emerging genomic and proteomic markers that are shaping current research. The clinical applicability of these markers is highlighted, and their role in improving diagnostic accuracy, predicting surgical outcomes, and monitoring response to treatment is demonstrated. The review also highlights the need for further research, including validation of these markers in larger studies, development of standardized assays, and integration with imaging techniques. The evolving field of biochemical markers holds promise for improving patient outcomes in the treatment of NENs, although challenges in standardization and validation remain.
PubMed: 38928704
DOI: 10.3390/diagnostics14121289 -
International Journal of Developmental... Jun 2024Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder...
Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder (ASD) often experience gastrointestinal problems and dysbiosis in their gut microbiota. Our previous study revealed that SMPS interventions had an impact on the gut microbiota of valproic acid (VPA)-induced autism model rats. However, the effects of SMPS on the behavior and gut function of autism model rats remain poorly understood. Therefore, we gave different doses of SMPS intervention in the early stage of autism model rats to observe their developmental conditions and behavior performances. Through histological evaluation and real-time polymerase chain reaction (PCR), integrity of the intestinal structure and the expression of tight junction-related gene Zo-1 and Occludin were detected. The results indicated that SMPS intervention improved the physical development, learning and memory impairment, and social performance of autism model rats. Meanwhile, SMPS promoted intestinal peristalsis and restored the integrity of the intestinal structure, reduced the number of inflammatory cells, and increased the expression of the Zo-1 and Occludin genes. Furthermore, the expression levels of neurotransmitters (substance P, enkephalin, vasoactive intestinal peptide, and 5-hydroxytryptamine) in the hippocampal tissues were altered after SMPS treatment. In conclusion, SMPS could ameliorate ASD-like phenotypes and gut problems in autism model rats. Collectively, these results provide new evidence for the relationship between the gut-brain axis and ASD and suggest a novel therapeutic target for ASD treatment.
PubMed: 38923604
DOI: 10.1002/jdn.10354 -
BJOG : An International Journal of... Jun 2024Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains...
OBJECTIVE
Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes.
DESIGN
Superiority, double-blind randomised controlled trial.
SETTING
A total of 20 UK fetal medicine units.
POPULATION
Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end-diastolic flow in the umbilical artery between 22 and 29 weeks of gestation.
METHODS
Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation.
MAIN OUTCOME MEASURES
All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score of >85.
RESULTS
In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow-up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4-50.3, vs 47.2 cm, 95% CI 44.7-48.9 cm).
CONCLUSIONS
Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition.
PubMed: 38923115
DOI: 10.1111/1471-0528.17888 -
Journal of Cardiovascular Pharmacology Apr 2024Thrombin is a coagulation factor increased in pregnancy and further increased in preeclampsia (PE), a hypertensive disorder. Thrombin is also expressed in brain and may...
Thrombin is a coagulation factor increased in pregnancy and further increased in preeclampsia (PE), a hypertensive disorder. Thrombin is also expressed in brain and may have a nonhemostatic role. We characterized thrombin expression and vasoactivity in brain cerebral parenchymal arterioles (PAs) in rat models of pregnancy and PE. PAs were isolated and pressurized from nonpregnant (NP), late-pregnant (LP) rats and rats with experimental preeclampsia (ePE). Reactivity to thrombin (1-50 U/mL) was measured in the absence and presence of inhibition of cyclooxygenase (COX) and nitric oxide synthase (NOS). Plasma levels of prothrombin, thrombin-antithrombin (TAT), tissue plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) and cerebrospinal fluid (CSF) levels of TAT were compared via ELISA. Expression of protease-activated receptor (PAR) types 1 and 2 in PAs were measured by Western blot and immunohistochemistry. Neuronal thrombin expression was quantified in brains from all groups by immunohistochemistry. Prothrombin and TAT were elevated in ePE plasma compared to NP and LP. TAT was detected in CSF from all groups and significantly elevated in LP (NP: 0.137±0.014 ng/mL, LP: 0.241±0.015 ng/mL, ePE: 0.192±0.028 ng/mL; p<0.05). Thrombin caused modest vasoconstriction in PAs from all groups regardless of COX or NOS inhibition. PAR1 and PAR2 were found in PAs from all groups co-localized to smooth muscle. Thrombin expression in central neurons was decreased in both LP and ePE groups compared to NP. These findings suggest a role for thrombin and other hemostatic changes during pregnancy and PE beyond coagulation.
PubMed: 38922586
DOI: 10.1097/FJC.0000000000001579 -
Journal of the Saudi Heart Association 2024Incidence and outcomes of acute kidney injury (AKI) among neonates who underwent open-heart surgery are not well highlighted in the literature. We aim to assess the...
BACKGROUND
Incidence and outcomes of acute kidney injury (AKI) among neonates who underwent open-heart surgery are not well highlighted in the literature. We aim to assess the incidence, risk factors, and outcome of AKI among neonates undergoing open-heart surgery.
METHODS
This is a retrospective cohort study between 2016 and 2021 for all neonates requiring open heart surgery. The cases were divided into 2 groups: the AKI (index) group and the non-AKI (control) group. The two groups were statistically compared for risk factors, needs for dialysis, and outcomes.
RESULTS
100 patients fulfilled the inclusion criteria. Among them, 74 (74%) developed AKI, including 41 (55%), 15 (21%), and 18 (24%) patients in KDIGO stages 1, 2, and 3, respectively. Multivariate analysis comparing both groups demonstrated that low pre-operative creatinine (p = 0.01), prolonged bypass time (p = 0.0004) and high vasoactive inotropic score (VIS), (p = 0.0008) were risk factors for developing AKI post-operatively. Furthermore, in the AKI group, 17 (23%) neonates required renal replacement therapy in the form of peritoneal dialysis. The length of stay was higher in the AKI index group (p = 0.015). Patients who had AKI recovered their kidney function at discharge. There was no difference in mortality between both groups.
CONCLUSION
The AKI occurred in 74% of neonates undergoing open-heart surgery, with 23% of them needing peritoneal dialysis. Low pre-operative creatinine, high VIS score, and prolonged bypass time are potential risk factors for AKI development after neonatal open-heart surgery. AKI may lead to prolonged hospitalization, though most affected patients recovered their normal kidney function at discharge.
PubMed: 38919507
DOI: 10.37616/2212-5043.1374 -
Pediatric Cardiology Jun 2024Phase 1 trials are primarily conducted to evaluate the safety and feasibility of new interventions, usually without recruiting control patients. This retrospective study...
Establishing Optimal Control Cohorts for Phase 1 Trials: Retrospective Analysis of Clinical and Biological Outcomes in Neonates and Infants Undergoing Two-Ventricle Repair.
Phase 1 trials are primarily conducted to evaluate the safety and feasibility of new interventions, usually without recruiting control patients. This retrospective study aims to characterize clinical and biological outcomes in historical and contemporary cases of neonates and infants undergoing two-ventricle repair to facilitate future secondary endpoint analyses for such trials. This retrospective study included neonates/infants (ages ≤ 6 months) who underwent two-ventricle repair between 2015 and 2021 using the same criteria as our phase 1 trial (n = 199). Patients were allocated into the ventricular septal defect (n = 61), the Tetralogy of Fallot (TOF, n = 88), and the transposition of the great arteries (n = 50) groups with an additional comparison between two eras (2015-2019 vs. 2020-2021). Patient characteristics and most variables assessed were different between the three diagnostic groups indicating the importance of diagnostic matching for secondary analyses. Although the era did not alter cerebral/somatic oxygenation, ventricular function, neuroimaging findings, and complication rates, we observed improvement of inotropic and/or vasoactive-inotropic scores in all groups during the more recent era. In 2020-2021, the age and the body weight at the operation were higher, and hospital stay was shorter in the TOF group, suggesting the possible impact of the pandemic. Results also indicated that matching altered characteristics such as age at operation that may limit the temporal effects and optimize secondary analyses. Using optimal contemporary cases and historical data based on this study will assist in developing a comprehensive study design for a future efficacy/effectiveness trial.
PubMed: 38918239
DOI: 10.1007/s00246-024-03550-5 -
Frontiers in Physiology 2024Efficient distribution of oxygen (O) to the tissues in mammals depends on the evolved ability of red blood cell (RBC) hemoglobin (Hb) to sense not only O levels, but... (Review)
Review
Efficient distribution of oxygen (O) to the tissues in mammals depends on the evolved ability of red blood cell (RBC) hemoglobin (Hb) to sense not only O levels, but metabolic cues such as pH, PCO, and organic phosphates, and then dispense or take up oxygen accordingly. O delivery is the product of not only oxygen release from RBCs, but also blood flow, which itself is also governed by vasoactive molecular mediators exported by RBCs. These vascular signals, including ATP and S-nitrosothiols (SNOs) are produced and exported as a function of the oxygen and metabolic milieu, and then fine-tune peripheral metabolism through context-sensitive vasoregulation. Emerging and repurposed RBC-oriented therapeutics can modulate either or both of these allosteric and vasoregulatory activities, with a single molecule or other intervention influencing both arms of O transport in some cases. For example, organic phosphate repletion of stored RBCs boosts the negative allosteric effector 2,3 biphosphoglycerate (BPG) as well as the anti-adhesive molecule ATP. In sickle cell disease, aromatic aldehydes such as voxelotor can disfavor sickling by increasing O affinity, and in newer generations, these molecules have been coupled to vasoactive nitric oxide (NO)-releasing adducts. Activation of RBC pyruvate kinase also promotes a left shift in oxygen binding by consuming and lowering BPG, while increasing the ATP available for cell health and export on demand. Further translational and clinical investigation of these novel allosteric and/or vasoregulatory approaches to modulating O transport are expected to yield new insights and improve the ability to correct or compensate for anemia and other O delivery deficits.
PubMed: 38915775
DOI: 10.3389/fphys.2024.1394650 -
General and Comparative Endocrinology Jun 2024The physiological processes in animal production are regulated through biologically active molecules like peptides, proteins, and hormones identified through the... (Review)
Review
The physiological processes in animal production are regulated through biologically active molecules like peptides, proteins, and hormones identified through the development of the fundamental sciences and their application. One of the main polypeptides that plays an essential role in regulating physiological responses is the pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP belongs to the glucagon/growth hormone-releasing hormone (GHRH)/vasoactive intestinal proteins (VIP) family and regulates feed intake, stress, and immune response in birds. Most of these regulations occur after PACAP stimulates the cAMP signaling pathway, which can regulate the expression of genes like MuRF1, FOXO1, Atrogin 1, and other ligases that are essential members of the ubiquitin system. On the other hand, PACAP stimulates the secretion of CRH in response to stress, activating the ubiquitin signaling pathway that plays a vital role in protein degradation and regulates oxidative stress and immune responses. Many studies conducted on rodents, mammals, and other models confirm the regulatory effects of PACAP, cAMP, and the ubiquitin pathway; however, there are no studies testing whether PACAP-induced cAMP signaling in poultry regulates the ubiquitin pathway. Besides, it would be interesting to investigate if PACAP can regulate ubiquitin signaling during stress response via CRH altered by HPA axis stimulation. Therefore, this review highlights a summary of research studies that indicate the potential interaction of the PACAP and ubiquitin signaling pathways on different molecular and physiological parameters in poultry species through the cAMP and stress signaling pathways.
PubMed: 38914296
DOI: 10.1016/j.ygcen.2024.114577 -
Journal of Cardiothoracic and Vascular... Jun 2024The current work was designed to compare the effects of ciprofol and propofol on left ventricular systolic function and myocardial work by noninvasive speckle-tracking...
Effect of Ciprofol on Left Ventricular Myocardial Strain and Myocardial Work in Children Undergoing Cardiac Surgery: A Single-center Double-blind Randomized Noninferiority Study.
OBJECTIVE
The current work was designed to compare the effects of ciprofol and propofol on left ventricular systolic function and myocardial work by noninvasive speckle-tracking echocardiography in children undergoing surgical repair of atrial septal or ventricular septal defects.
DESIGN
A single-center double-blind randomized noninferiority study was conducted.
SETTING
The research occurred at a tertiary care center affiliated with Shanghai Jiao Tong University, China.
PARTICIPANTS
One hundred and twelve children aged 1 month to 16 years undergoing atrial septal or ventricular septal defect surgery with cardiopulmonary bypass were included.
INTERVENTIONS
One hundred and twelve children were allocated randomly to receive ciprofol (n = 67) or propofol (n = 45) in a 1.5:1 ratio. Ciprofol or propofol were intravenously infused at loading doses of 0.4 mg/kg or 2.0 mg/kg, respectively, over 30 seconds, depending on the physical condition of each patient. When the bispectral index was maintained between 45 and 55 after induction, transthoracic echocardiography, including apical two-chamber, three-chamber, and four-chamber views, were collected bedside.
MEASUREMENTS AND MAIN RESULTS
Of the 112 patients enrolled, 104 completed the study. Global longitudinal strain in the ciprofol and propofol groups after anesthesia was -17.3% (95% confidence interval [CI] -18.0% to -16.6%) and -17.8% (95% CI -18.7 to -17.0%) in the full analysis set and -17.5% (95% CI -18.2% to -16.9%) and -17.8% (95% CI -18.7% to -17.0%) in the per-protocol set, respectively. The noninferiority margin was set at 2% and confirmed with a lower limit of two-sided 95% CI for the intergroup difference of 1.58% in the full analysis set and 1.34% in the per-protocol set. There were no significant differences between the groups in left ventricular systolic and diastolic function and myocardial work indices. Postoperative vasoactive-inotropic score, NT-proBNP, duration of mechanical ventilation, and the length of stay in the cardiac intensive care unit and hospital were also comparable between the two groups (all p > 0.05).
CONCLUSIONS
Ciprofol did not show different effects on myocardial function and postoperative outcomes from propofol. Further, on the sensitive cardiac systole marker global longitudinal strain, ciprofol demonstrated noninferiority to propofol. Ciprofol might be an alternative solution for cardiac anesthesia in children with congestive heart disease with mild lesion.
PubMed: 38908938
DOI: 10.1053/j.jvca.2024.05.036 -
ASAIO Journal (American Society For... Jun 2024Target values for arterial carbon dioxide tension (PaCO2) in extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) are unknown. We...
Target values for arterial carbon dioxide tension (PaCO2) in extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) are unknown. We hypothesized that lower PaCO2 values on ECMO would be associated with lighter sedation. We used data from two independent patient cohorts with ARDS spending 1,177 days (discovery cohort, 69 patients) and 516 days (validation cohort, 70 patients) on ECMO and evaluated the associations between daily PaCO2, pH, and bicarbonate (HCO3) with sedation. Median PaCO2 was 41 (interquartile range [IQR] = 37-46) mm Hg and 41 (IQR = 37-45) mm Hg in the discovery and the validation cohort, respectively. Lower PaCO2 and higher pH but not bicarbonate (HCO3) served as significant predictors for reaching a Richmond Agitation Sedation Scale (RASS) target range of -2 to +1 (lightly sedated to restless). After multivariable adjustment for mortality, tracheostomy, prone positioning, vasoactive inotropic score, Simplified Acute Physiology Score (SAPS) II or Sequential Organ Failure Assessment (SOFA) Score and day on ECMO, only PaCO2 remained significantly associated with the RASS target range (adjusted odds ratio 1.1 [95% confidence interval (CI) = 1.01-1.21], p = 0.032 and 1.29 [95% CI = 1.1-1.51], p = 0.001 per mm Hg decrease in PaCO2 for the discovery and the validation cohort, respectively). A PaCO2 ≤40 mm Hg, as determined by the concordance probability method, was associated with a significantly increased probability of a sedation level within the RASS target range in both patient cohorts (adjusted odds ratio = 2.92 [95% CI = 1.17-7.24], p = 0.021 and 6.82 [95% CI = 1.50-31.0], p = 0.013 for the discovery and the validation cohort, respectively).
PubMed: 38905594
DOI: 10.1097/MAT.0000000000002255