Search Results (21)

The image represents the post-mortem heart of a 28-year-old female patient, diagnosed in childhood with complete common atrioventricular canal defect. At time of diagnosis, the family refused surgery, as did the patient during her adulthood. Despite being advised against pregnancy, she became pregnant. On presentation to hospital, she was cyanotic, with clubbed fingers, and hemodynamically unstable, in sinus rhythm, with Eisenmenger syndrome and respiratory failure partially responsive to oxygen. During pregnancy, owing to systemic vasodilatation, the right-to-left shunt is increased, with more severe cyanosis and low cardiac output. Echocardiography revealed the complete common atrioventricular canal defect, with a single atrioventricular valve with severe regurgitation, right ventricular hypertrophy, pulmonary artery dilatation, severe pulmonary hypertension and a hypoplastic left ventricle. The gestational age at delivery was 38 weeks. She gave birth to a healthy boy, with an Apgar score of 10. The vaginal delivery was chosen by an interdisciplinary team. The cesarean delivery and the anesthesia were considered too risky compared to vaginal delivery. Three days later, the patient died. The autopsy revealed hepatomegaly, a greatly hypertrophied right ventricle with a purplish clot ascending the dilated pulmonary arteries and a hypoplastic left ventricle with a narrowed chamber. A single valve was observed between the atria and ventricles, making all four heart chambers communicate, also insufficiently developed interventricular septum and its congenital absence in the cranial third. These morphological changes indicate the complete common atrioventricular canal defect, with right ventricular dominance, which is a rare and impressive malformation that requires mandatory treatment in early childhood in order for the condition to be solved. Full article

Recent advancements in photovoltaic (PV) and battery technologies, combined with improvements in power electronic converters, have accelerated the adoption of rooftop PV systems and electric vehicles (EVs) in distribution networks, while these technologies offer economic and environmental benefits and support the transition to sustainable energy systems, they also introduce operational challenges, including voltage fluctuations, increased system losses, and voltage regulation issues under high penetration levels. Traditional Voltage and Var Control (VVC) strategies, which rely on substation on-load tap changers, voltage regulators, and shunt capacitors, are insufficient to fully manage these challenges. This study proposes a novel Voltage, Var, and Watt Control (VVWC) framework that coordinates the operation of PV and EV resources, conventional devices, and demand responsive loads. A mixed-integer nonlinear multi-objective optimization model is developed, applying a Chebyshev goal programming approach to balance objectives that include minimizing PV curtailment, reducing system losses, flattening voltage profile, and minimizing demand not met. Unserved demand has, in particular, been modeled while incorporating the concepts of distributional and recognition energy justice. The proposed method is validated using a modified version of the IEEE 123-bus test distribution system. The results indicate that the proposed framework allows for high levels of PV and EV integration in the grid, while ensuring that EV demand is met and PV curtailment is negligible. This demonstrates an equitable access to energy, while maximizing renewable energy usage. Full article

Background: Severe neonatal Ebstein’s anomaly (EA) is associated with a high risk of mortality. A new therapeutic approach aims to combine the advantages of Starnes’ procedure in stabilizing critically ill neonates with the long-term superiority of biventricular physiology after cone reconstruction. Case report: The echocardiography of a male preterm (36 weeks’ gestation; birth weight 2400 g) demonstrated EA Carpentier type C, membranous pulmonary atresia, and hypoplastic pulmonary arteries (PAs). After undergoing the Starnes procedure postnatally, multiple dilatations of the AP shunt and the Starnes fenestration followed. Cone reconstruction was performed at 15 months of age. Surgical revision addressed tricuspid and pulmonary valve insufficiency and PA bifurcation stenosis. Subsequently, PA branch stenosis with severe impairment of right ventricular function and dilatation required stent implantation. At the last follow-up, at 3 years of age, the patient was asymptomatic with sufficient exercise tolerance. Discussion: The American Association for Thoracic Surgery recently recommended evaluating all Starnes patients for potential conversion to cone. Consequently, the Starnes procedure should be modified to facilitate subsequent biventricular correction. Both the optimal timing of conversion and the appropriate assessment to reliably evaluate feasibility and the prospects for success require further investigation. Conclusions: Conversion from Starnes to cone is technically feasible, even in cases of severe EA, prematurity, low birth weight, and additional cardiac comorbidities, and provides promising initial results. Further research is needed to define candidacy and the optimal timing of conversion, and to assess long-term outcomes. The high therapeutic effort and complexity make this treatment approach suitable only for quaternary centers. Full article

When a 35 kV distribution network has the problem of insufficient reactive power, the input of a shunt reactor is a common compensation method. Vacuum circuit breakers are widely used in 35 kV distribution networks because of their superior arc extinguishing performance and convenient maintenance. However, in recent years, accidents involving vacuum circuit breakers breaking shunt reactors have occurred more frequently in China, such as high-frequency phase-to-phase short circuits, inter-turn burning losses, bus outlet short circuits, etc., which can cause serious damage and pose a greater threat to the safety of the power system. This paper focuses on the switching overvoltage generated by the vacuum circuit breaker cutting off the shunt reactor. Firstly, the mechanism of overvoltage generation is analyzed theoretically. It is concluded that the equivalent chopping current of the other two phases caused by the continuous reignition of the first open phase is the root cause of the high-amplitude interphase overvoltage. Based on the MODELS custom programming module in EMTP/ATP, according to the process of breaking and reigniting the circuit breaker, this paper uses Fortran language to compile the program and establishes a model of a vacuum circuit breaker, including power frequency current interception, high-frequency current, zero-crossing, breaking, and arc reignition modules. The vacuum circuit breaker is simulated for hundreds of continuous reignitions in milliseconds. Finally, a simulation study on the overvoltage suppression measures of a 35 kV shunt reactor is carried out. The comprehensive comparison of various suppression measures provides a reference for the reasonable selection of actual engineering conditions. Full article

To evaluate the effectiveness of the PRESERFLO MicroShunt (PFM) in reducing intraocular pressure (IOP) ex vivo in porcine eyes using an infusion pump system and to simulate various IOP conditions, In this study, porcine eyes received increasing flows between 2 and 20 μL/min. IOP measurements were taken under conditions with and without the PFM [PFM (+) and PFM (−), respectively]. In the PFM (−) group, IOP increased from 7.4 mmHg to 46.3 mmHg as the flow rate increased from 2 μL/min to 20 μL/min. The rate of IOP reduction (%ΔIOP) rose with increasing flow rates, although the absolute IOP values achieved with the PFM insertion also increased. The correlation between IOPs in the PFM (−) conditions and the %ΔIOP was modeled as %ΔIOP = 22.4 Ln [PFM(−) IOP] − 41.7. According to this equation, IOP reduction by PFM insertion is 0% at IOPs of 6.4 mmHg or lower. IOP reductions of 10%, 20%, 30%, and 40% were observed when the pre-insertion IOPs were 10.1, 15.7, 24.6, and 38.4 mmHg, respectively. Achievable post-insertion IOP levels of ≤21 mmHg, ≤18 mmHg, ≤15 mmHg, and ≤12 mmHg corresponded to the initial IOPs of 33 mmHg, 26 mmHg, 20 mmHg, and 14.8 mmHg, respectively. In conclusion, the PFM effectively reduced IOP within a specific range of IOP values in an ex vivo experimental system. In clinical situations, the PFM is unlikely to be effective at low IOP levels. At higher levels, the PFM reduces IOP, but it may be insufficient to achieve the target IOP. Full article

Congenital portosystemic shunts (CPSS) are vascular anomalies resulting in liver hypoplasia and hepatic insufficiency. Cats with CPSS typically show signs of hepatic encephalopathy associated with increased ammonia, inflammatory cytokines, and oxidative stress. Surgical attenuation of the CPSS results in improved liver function, resolution of clinical signs, and increased portal blood flow. Hepatic gene expression has not previously been investigated in cats with CPSS. Here, we compared the hepatic expression of genes involved in the urea cycle (CPS1, NAGS), angiogenesis (VEGFR2, NPPA, NPR1, NPPC, NPR2, HIF1a), liver regeneration (SERPINB1, HGF, TGFβ), and metabolism (FGF21) from a small series of cats (n = 18) with CPSS to that of control cats (n = 10). The expression of TGFβ, VEGFR2, HGF, FGF21, and CPS1 was significantly elevated in liver biopsies from cats with CPSS. Cats that could only tolerate partial closure of their CPSS had increased hepatic expression of SERPINB1, HIF1a, and NPR2 compared with those that could tolerate complete ligation. Furthermore, there were no significant correlations between gene expression and pre-operative plasma ammonia concentrations in cats with CPSS. The changes in hepatic gene expression in cats with CPSS are in direct contrast to those seen in dogs with CPSS, suggesting alternative mechanisms may be involved in mediating hepatic changes in cats with CPSS. Full article

Background: Tracheoesophageal shunt insufficiency (TESI) is a common and potentially life-threatening complication after laryn(-gopharyn)gectomy (L(P)E). We investigated whether TESI could be the result of a specific shunt location. Methods: A monocentric, retrospective cohort analysis of 171 consecutively treated L(P)E patients was performed. Patients with a secondary prosthesis instillation and patients with insufficient postoperative imaging were excluded. Disease related data as well as location of primary voice prosthesis were assessed. Results: The cohort was divided into 62 TESI-positive and 109 TESI-negative individuals. The mean time from surgery to TESI was 32 months. No differences were observed in gender, age, tumor localization, T/R/M-status. Surgery without adjuvant therapy was more often performed in TESI-negative individuals when compared with their positive counterparts. However, Cox regression including T/N status, therapy and categorized distance of the tracheoesophageal shunt to the manubrium (≤1.5 cm vs. >1.5 cm) revealed that a distance of ≤1.5 cm was associated with a 2.1-fold increased risk of TESI, while all other parameters did not influence the event-free survival. Conclusions: Primary shunt positioning ≤1.5 cm to the ridge of the manubrium is associated with an increased risk of TESI. In these individuals secondary shunt operation resulting in a position >1.5 cm distant to the manubrium should be recommended. Full article

Infective endocarditis (IE) is common in patients with corrected congenital heart disease (CHD) with a residual lesion, but is rarely found on surgical patches used to close atrial septal defects (ASDs). This is also reflected in the current guidelines that do not recommend antibiotic therapy for patients with a repaired ASD with no residual shunt six months after closure (percutaneous or surgical). However, the situation could be different in the case of mitral valve endocarditis, which causes leaflet disruption with severe mitral insufficiency and could seed the surgical patch. We present herein a 40-year-old male patient with a past medical history of a complete surgically corrected atrioventricular canal defect performed in childhood who presented with fever, dyspnea and severe abdominal pain. Transthoracic and transesophageal echocardiography (TTE and TEE) revealed vegetation at the level of the mitral valve and the interatrial septum. The CT scan confirmed ASD patch endocarditis and multiple septic emboli, guiding the therapeutic management. An accurate evaluation of cardiac structures should be mandatory when a systemic infection is detected in CHD patients, even if the defects were surgically corrected, because the detection and eradication of such infectious foci as well as a surgical reintervention are particularly difficult to achieve in this subpopulation. Full article

Congenital portosystemic shunts (CPSS) are abnormal vascular communications between the portal and the systemic circulation, bypassing the hepatic parenchyma and resulting in liver hypoplasia and hepatic insufficiency. Such connections develop in utero and persist postnatally. CPSS are among the two most common congenital vascular anomalies of the liver in small animals, along with primary hypoplasia of the portal vein without portal hypertension (PHPV without PH). CPSS can be extrahepatic (ECPSS), most commonly diagnosed in small and toy breed dogs and cats, or intrahepatic (ICPSS), most commonly seen in large breed dogs. Single ECPSS is the most common type encountered in both dogs and cats. Clinical signs of CPSS are non-specific and may wax and wane, while laboratory findings can raise clinical suspicion for CPSS, but they are also not specific. Definitive diagnosis will be established by evaluation of liver function tests, such as determination of fasting plasma ammonia (FA) levels, and pre- and postprandial serum bile acids concentrations, and diagnostic imaging. The purpose of this article is to review the definition, classification, pathogenesis, clinical presentation, and diagnosis of CPSS in dogs and cats, highlighted by the authors’ clinical experience. Full article

Most interventionalists use the Amplatzer Duct Occluder (ADO) or the Nit-Occlud^® Coils (NOC) to close patent ductus arteriosus (PDA). Data regarding the success and effect of NOCs in the occlusion of large PDAs are insufficient. We aimed to investigate whether the PDA occlusion of large PDAs using NOC is safe and efficient for all ages. This was a retrospective study involving 361 pediatric and adult patients who underwent the transcatheter closure of PDA using NOC over the past 21 years for all PDA sizes and ages. The sizes of PDA were classified as small, moderate, and large. A comparison of the aortic pressure before and after PDA occlusion using NOC showed significant differences in terms of systolic and pulse pressures for all age groups (p < 0.05). The rate of the residual shunts of NOC was 2%, while the rate of complete occlusions of NOC was 98% at 12 months after occlusion regardless of the shape of PDA. The complication rate with PDA occlusion using NOC was 5%. PDA occlusion using NOC is as effective and safe as ADO for the occlusion of PDA of all sizes. Therefore, PDA occlusion using NOC can be a safe and feasible procedure to close various sizes and types of PDA without complications. Full article

It is increasingly likely that many non-communicable diseases of humans and associated animals are due to the degradation of their intestinal microbiomes, a situation often referred to as dysbiosis. An analysis of the resultant diseases offers an opportunity to probe the function of these microbial partners of multicellular animals. In our view, it now seems likely that vertebrate animals and their microbiomes have coevolved throughout the Ediacaran–Cambrian transition and beyond, operating by semiochemical messaging between the multicellular host and its microbial community guest. A consideration of the overall role of the mutualistic intestinal microbiome as an enclosed bioreactor throws up a variety of challenging concepts. In particular: the significance of the microbiome with respect to the immune system suggests that microeukaryotes could act as microbial sentinel cells; the ubiquity of bacteriophage viruses implies the rapid turnover of microbial composition by a viral-shunt mechanism; and high microbial diversity is needed to ensure that horizontal gene transfer allows valuable genetic functions to be expressed. We have previously postulated that microbes of sufficient diversity must be transferred from mother to infant by seemingly accidental contamination during the process of natural birth. We termed this maternal microbial inheritance and suggested that it operates alongside parental genetic inheritance to modify gene expression. In this way, the adjustment of the neonate immune system by the microbiome may represent one of the ways in which the genome of a vertebrate animal interacts with its microbial environment. The absence of such critical functions in the neonate may help to explain the observation of persistent immune-system problems in affected adults. Equally, granted that the survival of the guest microbiome depends on the viability of its host, one function of microbiome-generated semiochemicals could be to facilitate the movement of food through the digestive tract, effectively partitioning nutrition between host and guest. In the event of famine, downregulation of microbial growth and therefore of semiochemical production would allow all available food to be consumed by the host. Although it is often thought that non-communicable diseases, such as type 2 diabetes, are caused by consumption of food containing insufficient dietary fibre, our hypothesis suggests that poor-quality food is not the prime cause but that the tendency for disease follows the degradation of the intestinal microbiome, when fat build-up occurs because the relevant semiochemicals can no longer be produced. It is the purpose of this paper to highlight the possibility that the origins of the microbiome lie in the Precambrian and that the disconnection of body and microbiome gives rise to non-communicable disease through the loss of semiochemical signalling. We further surmise that this disconnect has been largely brought about by heavy metal poisoning, potentially illuminating a facet of the exposome, the sum total of environmental insults that influence the expression of the genetic inheritance of an animal. Full article

Bioreactor scale-up from the laboratory scale to the industrial scale has always been a pivotal step in bioprocess development. However, the transition of a bioeconomy from innovation to commercialization is often hampered by performance loss in titer, rate and yield. These are often ascribed to temporal variations of substrate and dissolved oxygen (for instance) in the environment, experienced by microorganisms at the industrial scale. Oscillations in dissolved oxygen (DO) concentration are not uncommon. Furthermore, these fluctuations can be exacerbated with poor mixing and mass transfer limitations, especially in fermentations with filamentous fungus as the microbial cell factory. In this work, the response of glucose-limited chemostat cultures of an industrial Penicillium chrysogenum strain to different dissolved oxygen levels was assessed under both DO shift-down (60% → 20%, 10% and 5%) and DO ramp-down (60% → 0% in 24 h) conditions. Collectively, the results revealed that the penicillin productivity decreased as the DO level dropped down below 20%, while the byproducts, e.g., 6-oxopiperidine-2-carboxylic acid (OPC) and 6-aminopenicillanic acid (6APA), accumulated. Following DO ramp-down, penicillin productivity under DO shift-up experiments returned to its maximum value in 60 h when the DO was reset to 60%. The result showed that a higher cytosolic redox status, indicated by NADH/NAD+, was observed in the presence of insufficient oxygen supply. Consistent with this, flux balance analysis indicated that the flux through the glyoxylate shunt was increased by a factor of 50 at a DO value of 5% compared to the reference control, favoring the maintenance of redox status. Interestingly, it was observed that, in comparison with the reference control, the penicillin productivity was reduced by 25% at a DO value of 5% under steady state conditions. Only a 14% reduction in penicillin productivity was observed as the DO level was ramped down to 0. Furthermore, intracellular levels of amino acids were less sensitive to DO levels at DO shift-down relative to DO ramp-down conditions; this difference could be caused by different timescales between turnover rates of amino acid pools (tens of seconds to minutes) and DO switches (hours to days at steady state and minutes to hours at ramp-down). In summary, this study showed that changes in oxygen availability can lead to rapid metabolite, flux and productivity responses, and dynamic DO perturbations could provide insight into understanding of metabolic responses in large-scale bioreactors. Full article

The RAF1:p.Ser257Leu variant is associated with severe Noonan syndrome (NS), progressive hypertrophic cardiomyopathy (HCM), and pulmonary hypertension. Trametinib, a MEK-inhibitor approved for treatment of RAS/MAPK-mutated cancers, is an emerging treatment option for HCM in NS. We report a patient with NS and HCM, treated with Trametinib and documented by global RNA sequencing before and during treatment to define transcriptional effects of MEK-inhibition. A preterm infant with HCM carrying the RAF1:p.Ser257Leu variant, rapidly developed severe congestive heart failure (CHF) unresponsive to standard treatments. Trametinib was introduced (0.022 mg/kg/day) with prompt clinical improvement and subsequent amelioration of HCM at ultrasound. The appearance of pulmonary artery aneurysm and pulmonary hypertension contributed to a rapid worsening after ventriculoperitoneal shunt device placement for posthemorrhagic hydrocephalus: she deceased for untreatable CHF at 3 months of age. Autopsy showed severe obstructive HCM, pulmonary artery dilation, disarrayed pulmonary vascular anatomy consistent with pulmonary capillary hemangiomatosis. Transcriptome across treatment, highlighted robust transcriptional changes induced by MEK-inhibition. Our findings highlight a previously unappreciated connection between pulmonary vascular disease and the severe outcome already reported in patients with RAF1-associated NS. While MEK-inhibition appears a promising therapeutic option for HCM in RASopathies, it appears insufficient to revert pulmonary hypertension. Full article

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunting. HE manifests as a spectrum of neurological or psychiatric abnormalities. Diagnosis of overt HE (OHE) is based on the typical clinical manifestation, but covert HE (CHE) has only very subtle clinical signs and minimal HE (MHE) is detected only by specialized time-consuming psychometric tests, for which there is still no universally accepted gold standard. Significant progress has been made in artificial intelligence and its application to medicine. In this review, we introduce how artificial intelligence has been used to diagnose minimal hepatic encephalopathy thus far, and we discuss its further potential in analyzing speech and handwriting data, which are probably the most accessible data for evaluating the cognitive state of the patient. Full article

A 2-year-old Boxer with a history of subaortic stenosis and immunosuppressant therapy developed aortic valve infective endocarditis. On echocardiographic examination with simultaneous electrocardiographic tracing, multiple uncommon periannular complications of the aortic valve endocarditis were found, including aorto-cavitary fistula with diastolic left-to-right shunt, tricuspid valve endocarditis, and third-degree atrioventricular block. Necropsy confirmed the above echocardiographic findings. Although aortic valve endocarditis represents a well-known disease entity in dogs, the dynamic nature of this condition may allow development of complex and uncommon echocardiographic features. Full article