Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

Endoscopic retrograde cholangiopancreatography (ERCP) is a routinely used therapeutic procedure for the biliary and pancreatic diseases. Population aging may increase the typical indications of ERCP and come with more complexity and difficulties, especially in cannulation. This study aimed to evaluate the incidence, causes, and management of difficult biliary cannulation during ERCP in super-aged patients and the role of difficult cannulation as a risk factor for adverse events. A total of 614 patients, underwent ERCP, were prospectively studied as a cohort and divided into two groups based on their age. There were 146 patients aged 80 years or older in group A and 468 patients aged less than 80 years in group B. The primary outcome measures were the difficulty grade of papilla cannulation, clinical outcomes, and ERCP-related complications in the two groups. The adverse events were analyzed using logistic regression for patient age, co-morbidities, indications, and cannulation difficulty grade variables. There was no difference in the incidence of difficult cannulation between the two groups (32.9% vs. 34.4%, p=0.765) though, as expected, super-aged Group A had a higher prevalence of periampullary diverticulum (29.5% vs. 16.7%, p=0.001). The technical cannulation success rate was (96.6% vs. 96.8%, p= 0.54). All used cannulation techniques in the elderly group were efficient and safe. Logistic regression showed that age ≥80 was not associated with increased adverse events; however, difficult cannulation (adjusted odds ratio [AOR]=3.478; 95% confidence interval [CI]=1.877, 6.442; p<0.001) and CCI ≥2 (AOR=1.824; 95% CI=0.993, 3.349; p=0.045) were more likely to have adverse events. Age ≤65 (AOR=3.460; 95% CI=1.511, 7.922; p=0.003), female gender (AOR=2.362; 95% CI=1.089, 5.124; p=0.030), difficult cannulation (AOR=4.527; 95% CI=2.078, 9.860; p<0.001), and patients with cholangitis (AOR=3.261; 95% CI=1.204, 8.832; p=0.020) were strongly associated with increasing Post-ERCP Pancreatitis (PEP). Advanced age has not proved to be a risk factor of difficult cannulation, and secondary cannulation techniques can be safely and efficaciously utilized for this group. CCI ≥2 and difficult cannulation are associated with increased overall adverse events rate while age ≥80 factor is not.

Aim: This study aimed to investigate the association between periampullary diverticulum (PAD) and difficult biliary cannulation, as well as to evaluate the impact of different types of PAD on the cannulation success rate and adverse events. Methods: A total of 636 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) during the study period were prospectively studied and divided into two groups based on the presence or absence of PAD. In group A, 126 patients had PAD compared with 510 patients in group B without PAD. The primary outcome measurements were ERCP procedures time, selective cannulation techniques, and cannulation difficulty in addition to cannulation success rate and ERCP-related adverse events. The difficult cannulation was analyzed using logistic regression considering age, co-morbidities, the presence of PAD types, and indications as independent factors. Results: The average cohort age was 65.30±16.67 years, and 52.7% were male. Significant higher rates of choledocholithiasis, cholangitis, and biliary pancreatitis were reported in the group of PAD (p<0.05). Successful selective cannulation was achieved in 97.6% in group A and 95.3% in group B (p>0.05). The cannulation time was significantly longer in the presence of PAD (5.1 min, vs. 4.09 min, p<0.05). There was no significant difference in the rate of overall adverse events and post ERCP pancreatic PEP. Conclusion: The presence of PAD did not affect the duration or success of the ERCP procedure. Furthermore, it was associated with longer cannulation time and increase in the cannulation difficulty, especially with PAD type 1.

Objective. Acute bowel ischemia is a life-threatening abdominal emergency. In many patients percutaneous endovascular repair of visceral arteries in an antegrade direction, across occluding plaques is challenging and sometimes not possible. Case Report. We present the case of technically successful percutaneous retrograde recanalization of occluded superior mesenteric artery in ctitically-ill 82-year-old patient. The superior mesenteric artery was recanalized via the branches of the celiac trunk; the guidewires were navigated to the target artery through the gastroduodenal and pancreatoduodenal arteries. Conclusion. Retrograde percutaneous recanalization of the superior mesenteric artery is technically feasible, even in hemodynamically unstable patients.

Human respiratory syncytial virus (hRSV) is the most common cause of bronchiolitis and pneumonia in new-borns, with all children being infected before the age of two. Reinfections are very common throughout life, and can cause severe respiratory infections in the elderly and immunocompromised adults. Although vaccines and preventive antibodies have recently been licensed for use in specific subpopulations of patients, there is still no therapeutic treatment commonly available for these infections. Here, we investigated the potential antiviral activity of Retro-2.2, a derivative of the cellular retrograde transport inhibitor Retro-2, against hRSV. We show that Retro-2.2 inhibits hRSV replication in cell culture, and impairs the ability of hRSV to form syncytia. Our results suggest that Retro-2.2 treatment affects virus spread by disrupting the trafficking of the viral de novo synthetized F and G glycoproteins to the plasma membrane, leading to a defect in virion morphogenesis. Taken together, our data show that targeting intracellular transport may be an effective strategy against hRSV infection.

Introduction: There is no standardised, universal method to assess physical conditions such as pressure in the pelvicalyceal system in real time during RIRS (retrograde intrarenal surgery). Therefore, the problem concerning increased pressure in the upper urinary tract during the procedure is underestimated. Moreover, it potentially may cause micro-damage and longer postoperative recovery. The aim of this study was to evaluate intrapelvic pressure (IPP) during RIRS procedures. Materials and methods: The 3D printed models of the pelvicalyceal system were printed based on CT-scan of real patient. They were used to perform 50 RIRS procedures with laser lithotripsy of artificially synthesised kidney stones with two different sizes of ureteral access sheath-UAS (10/12Fr vs. 12/14Fr) together with different energy settings generated by the holmium:YAG laser. IPP monitoring during RIRS was performed with the use of the PressureWire X Guidewire compatible with the CoroFlow system. Results and Conclusions: The results showed that high IPP of up to 400 cmH2O would be achieved using a 10/12Fr UAS, while the use of a 12/14Fr UAS would significantly reduce the peak pressure to approximately 100 cmH2O, hence the size of the UAS is a pivotal factor of the IPP generated during the procedure.

This paper presents research on the application of trajectory design, optimization, and control to an orbital transfer from Mars-Phobos Distant Retrograde Orbits to the surface of Phobos. Given a Distant Retrograde Orbits and a landing location on the surface of Phobos, landing trajectories for which total Δv for a direct 2-burn maneuver is minimized are computed. This is accomplished through the use of Particle Swarm Optimization in which the required Δv and time of flight are optimization parameters. The non-uniform gravitational environment of Phobos is considered in the computation. Results show how direct transfers can be achieved with Δv in the order of ∼30 m/s.

Distant Retrograde Orbits in the Earth-Moon system are gaining in popularity as stable `parking' orbits for various conceptual missions. To investigate the stability of potential Distant Retrograde Orbits, simulations were executed, with propagation running over a thirty-year period. Initial conditions for the vehicle state were limited such that the position and velocity vectors were in the Earth-Moon orbital plane, with the velocity oriented such that it would produce retrograde motion about Moon. The resulting trajectories were investigated for stability against the eccentric relative orbits of Earth and Moon in an environment that also included gravitational perturbations from Sun, Jupiter, and Venus, and the effects of radiation pressure. The results appear to indicate that stability is enhanced for certain resonant states within the Earth-Moon system.

Background: Endoscopic sphincterotomy (EST) has been employed for the endoscopic treatment of common bile duct stones (CBDSs), and a high success rate of stone removal has been reported. However, EST is associated with the risk of bleeding, perforation, and sphincter of Oddi function disruption. To avoid these risks, endoscopic papillary balloon dilation (EPBD) is an option for CBDS. Sphincter of Oddi function preservation decreases long-term biliary infection and gallstone recurrence. EPBD may have advantages in children who require a long follow-up. However, there have been few reports on pediatric cases, particularly in infants. Methods: From September 2017 to December 2023, we performed EPBD for four pediatric CBDSs. The patients were aged from 5 months to 8 years; including two infants aged 5 and 6 months. Furthermore, we reviewed the stone removal rate and complications of 545 ESTs performed at high-volume centers and 13 EPBD-reported cases in children with CBDSs. Results: CBDSs of all patients who underwent EPBD in our institution were successfully removed. No bleeding or perforation was noted, and pancreatitis was observed in three patients. In an analysis of 545 ESTs in children, the stone removal rate was high, ranging from 83% to 100% (mean, 96%). The incidence of pancreatitis was 0%–9.6% (mean, 4.4%), and the grade of pancreatitis was almost mild. The bleeding frequency was 1.3%–5.4% (mean, 2.7%). According to the grade of bleeding, seven and four cases were mild (64%) and moderate (36%), respectively, Compared with adult cases who underwent EST, the frequency of pancreatitis and bleeding was almost similar in children.; however once bleeding occur, it has a higher risk of leading to blood transfusion in children. Stone removal by EPBD in children was 100% successful. All complications were pancreatitis, and its frequency was 46% (6/13 patients, including five mild cases and one moderate case), which is higher than that of EST and adult cases who underwent EPBD. In most children with pancreatitis, pancreatic enzyme levels returned to normal within 2–3 days following EPBD, and no severe cases caused by EPBD were reported. Conclusions: CBDS removal by EPBD in children has a high success rate with very low risk of bleeding and perforation. Although pancreatitis frequently occurs, most cases are mild. Sphincter of Oddi function preservation by EPBD is expected to prevent long-term stone recurrence and biliary tract infection, and EPBD is considered an effective method for CBDS removal in children.

It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

Without protective and/or therapeutic agents the SARS-CoV-2 infection known as coronavirus disease 2019 (COVID-19) is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body crosstalk between organs. The majority of SARS-CoV-2 infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial-barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.