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Background: Acute myeloid leukemia (AML) is characterized by the abnormal proliferation of myeloid precursor cells and presents significant challenges in treatment due to its heterogeneity. Recently, the NLRP3 inflammasome has emerged as a potential contributor to AML pathogenesis, although its precise mechanisms remain poorly understood., Methods: Public genome datasets were utilized to evaluate the expression of NLRP3 inflammasome-related genes (IL-1β, IL-18, ASC, and NLRP3) in AML patients compared to healthy individuals. CRISPR/Cas9 technology was employed to generate NLRP3-deficient MOLM-13 AML cells, followed by comprehensive characterization using real-time PCR, western blotting, FACS analysis, and transmission electron and immunofluorescence microscopy. Proteomic analyses were conducted to identify NLRP3-dependent alterations in protein levels, with a focus on the eIF2 kinase PERK-mediated signaling pathways. Additionally, in vivo studies were performed using a leukemic mouse model to elucidate the pathogenic role of NLRP3 in AML., Results: Elevated expression of NLRP3 was significantly associated with diminished overall survival in AML patients. Genetic deletion, pharmacological inhibition and silencing by RNA interference of NLRP3 led to decreased AML cell survival through the induction of apoptosis. Proteomic analyses uncovered NLRP3-dependent alterations in protein translation, characterized by enhanced eIF2α phosphorylation in NLRP3-deficient AML cells. Moreover, inhibition of PERK-mediated eIF2α phosphorylation reduced apoptosis by downregulating pro-apoptotic Bcl-2 family members. In vivo studies demonstrated reduced leukemic burden in mice engrafted with NLRP3 knockout AML cells, as evidenced by alleviated leukemic symptoms., Conclusion: Our findings elucidate the involvement of the NLRP3/PERK/eIF2 axis as a novel driver of AML cell survival. Targeting NLRP3-induced signaling pathways, particularly through the PERK/eIF2 axis, presents a promising therapeutic strategy for AML intervention. These insights into the role of the NLRP3 inflammasome offer potential avenues for improving the prognosis and treatment outcomes of AML patients., (© 2024. The Author(s).)

Objective: To determine better in-office measures for artificial urinary sphincter outcomes, we investigated the ability of preoperative timed peg-transfer, pinch strength, grip strength, and Disabilities of the Arm Shoulder and Hand Outcome questionnaire in predicting postoperative satisfaction, confidence, and ease of use of artificial urinary sphincter placement for stress urinary incontinence., Materials and Methods: A timed 9-hole peg test, pinch and grip strength assessment, and upper extremity questionnaire were administered during the preoperative visit before sphincter placement. In addition to standard preoperative workup, short-form International Consultation of Incontinence Questionnaire and physician handshake were recorded. Activation occurred 6 weeks after surgery along with assessment of adequacy of pump placement. Three months from surgery a repeat incontinence questionnaire and a survey measuring satisfaction, difficulty of use, and confidence were given. Correlation between preoperative assessment variables and the postoperative questionnaire was assessed., Results: Thirty-nine patients were included. Average age and body mass index were 68.8 years and 28.8 kg/m 2 , respectively. Prior prostatectomy accounted for 92.3% of patients, and 46.2% had prior pelvic radiation. Postoperatively, 59.0% of patients were very satisfied; 64.1% of patients reported no difficulty of use; 53.8% felt confidence within 1 day; and 66.7% had much better bladder control. Average pad improvement count was 5.3. Pinch test was associated with satisfaction (P = .011) while peg test was associated with confidence (P = .049). Handshake and upper extremity questionnaire were not significant., Conclusion: The pinch and 9-hole peg transfer tests are cost-effective and easily performed adjuncts that could be used during artificial urinary sphincter evaluation for patients with unclear manual functional status., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rotavirus (RV) replicates within viroplasms, membraneless electron-dense globular cytosolic inclusions with liquid-liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, VP1, VP2, VP3, and VP6), single- and double-stranded virus RNAs, and host components such as microtubules, perilipin-1, and chaperonins. The formation, coalescence, maintenance, and perinuclear localization of viroplasms rely on their association with the cytoskeleton. A stabilized microtubule network involving microtubules and kinesin Eg5 and dynein molecular motors is associated with NSP5, NSP2, and VP2, facilitating dynamic processes such as viroplasm coalescence and perinuclear localization. Key post-translation modifications, particularly phosphorylation events of RV proteins NSP5 and NSP2, play pivotal roles in orchestrating these interactions. Actin filaments also contribute, triggering the formation of the viroplasms through the association of soluble cytosolic VP4 with actin and the molecular motor myosin. This review explores the evolving understanding of RV replication, emphasizing the host requirements essential for viroplasm formation and highlighting their dynamic interplay within the host cell.

Rotavirus (RV) replication takes place in the viroplasms, cytosolic inclusions that allow the synthesis of virus genome segments and their encapsidation in the core shell, followed by the addition of the second layer of the virion. The viroplasms are composed of several viral proteins, including NSP5, which serves as the main building block. Microtubules, lipid droplets, and miRNA-7 are among the host components recruited in viroplasms. We investigated the interaction between RV proteins and host components of the viroplasms by performing a pull-down assay of lysates from RV-infected cells expressing NSP5-BiolD2. Subsequent tandem mass spectrometry identified all eight subunits of the tailless complex polypeptide I ring complex (TRiC), a cellular chaperonin responsible for folding at least 10% of the cytosolic proteins. Our confirmed findings reveal that TRiC is brought into viroplasms and wraps around newly formed double-layered particles. Chemical inhibition of TRiC and silencing of its subunits drastically reduced virus progeny production. Through direct RNA sequencing, we show that TRiC is critical for RV replication by controlling dsRNA genome segment synthesis, particularly negative-sense single-stranded RNA. Importantly, cryo-electron microscopy analysis shows that TRiC inhibition results in defective virus particles lacking genome segments and polymerase complex (VP1/VP3). Moreover, TRiC associates with VP2 and NSP5 but not with VP1. Also, VP2 is shown to be essential for recruiting TRiC in viroplasms and preserving their globular morphology. This study highlights the essential role of TRiC in viroplasm formation and in facilitating virion assembly during the RV life cycle., Importance: The replication of rotavirus takes place in cytosolic inclusions termed viroplasms. In these inclusions, the distinct 11 double-stranded RNA genome segments are co-packaged to complete a genome in newly generated virus particles. In this study, we show for the first time that the tailless complex polypeptide I ring complex (TRiC), a cellular chaperonin responsible for the folding of at least 10% of the cytosolic proteins, is a component of viroplasms and is required for the synthesis of the viral negative-sense single-stranded RNA. Specifically, TRiC associates with NSP5 and VP2, the cofactor involved in RNA replication. Our study adds a new component to the current model of rotavirus replication, where TRiC is recruited to viroplasms to assist replication., Competing Interests: The authors declare no conflict of interest.

Purpose: Though controversial, alpha blockers are used widely for ureteral stone passage. However, its effects on the patient-reported Quality of life (QOL) is unknown. We compared the QoL of patients on alpha-blocker medical expulsive therapy (MET) to patients not on MET (noMET) utilizing the validated Wisconsin Stone Quality of Life (WISQOL)., Methods: This prospective study included patients prescribed either MET or noMET after presentation with symptomatic, obstructing ureteral stones. The treatment arm was decided at the point of care by the initial treating physician and included analgesia and antiemetics. Tamsulosin (0.4 mg daily) was prescribed for the MET group. The WISQOL survey was administered at baseline, 7-, 14-, 21- and 28-days following discharge from the ED or until stone expulsion., Results: 197 patients were enrolled, of which 116 (59.2%) completed questionnaires for analysis, 91 in the MET group and 25 in noMET. Average ureteral stone size was 4.7 mm (SD 1.8) and 3.1 mm (SD 1.0) for MET and noMET, respectively. Of completed surveys, 105 (90%) were completed at day 7, 67 (57.6%) at day 14, 53 (45.7%) at day 21, and 40 (34.5%) at day 28. MET was associated with improved QoL scores across all WISQOL domains compared to noMET. Stone size, age, race, sex, comorbidity score and a prior stone history were not associated with reduced QoL., Conclusions: The use of MET was associated with improved QOL on all WISQOL metrics compared to noMET patients. Improved stone QOL may be an indication of alpha-blocker therapy in patients with ureteral stone colic., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Some patients with renal cell carcinoma (RCC) present with venous tumor thrombus (VTT). The extent of the VTT is related to survival, so prompt surgical care is recommended. However, studies evaluating the natural history of VTT in patients with RCC are rare. We sought to evaluate the growth kinetics of VTT in patients with RCC using preoperative cross-sectional images., Materials and Methods: We identified patients who underwent radical nephrectomy and venous tumor thrombectomy at our institution from 01/2009 to 02/2022. We included those with a minimum of 2 adequate preoperative imaging studies (contrast-enhanced Computerized Tomography (CT), noncontrast Magnetic resonance imaging (MRI), or contrast-enhanced MRI), at least 14 days apart. We measured VTT in each study to calculate growth rate, and evaluated predictors of faster growth (demographics, histology, laterality, tumor diameter, and staging). To assess the relation between clinical variables and VTT growth, we used the Wilcoxon Rank-Sum, Kruskal-Wallis, and Spearman correlation tests., Results: A total of 30 patients were included in the analysis. The median time interval between studies was 33 days. Patients were mostly Caucasian and Males (90% and 70%, respectively). Most patients underwent a CT scan as their initial imaging study (66%), followed with an MRI as second study (73%). The mean venous tumor thrombus growth rate was 0.3 mm/d (standard deviation of 0.5mm), and only rhabdoid/sarcomatoid differentiation showed an association with tumor thrombus growth rate (0.3 vs. 0.63 mm/d, P = 0.038)., Conclusions: To the best of our knowledge, this is the first study evaluating the natural growth rate of venous tumor thrombus in patients with renal cell carcinoma. We found that tumor thrombi grew an average of 0.3 mm/d (1.0 cm/month) and that those with sarcomatoid and/or rhabdoid differentiation grew faster (0.63 mm/d). Further studies are needed to validate these results and provide a better understanding of tumor thrombus kinetics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The necessity of nephrostomy tube after percutaneous nephrolithotomy (PCNL) has been called into question in modern series. We sought to examine differences in postoperative complications and outcomes of tubeless PCNL versus standard PCNL at our institution., Methods: A retrospective review of our institutional stone database was conducted from January 2016 to December 2021 for patients who had undergone either tubeless PCNL, defined by placement of only an internal ureteral stent, or standard PCNL, which involved placement of an externalized nephrostomy tube. Patients were excluded if they underwent totally tubeless PCNL., Results: A total of 438 patients were included for analysis: 329 patients underwent tubeless PCNL and 109 patients underwent standard PCNL. Between tubeless and standard groups, there was no difference in readmission rates 6.1% vs. 9.2% (p = 0.268), Clavien 2 or > complications 18.5% vs. 19.3% (p = 0.923), and Clavien 3 or > complications 4.0% vs. 7.3% (p = 0.151). The tubeless group experienced shorter operative duration 121.5 vs. 144.8 min (p = 0.012), shorter length of stay 2.5 vs. 3.8 days (p = 0.002), and higher stone-free rates 72.3% vs. 60.2% (p = 0.014), but also increased blood transfusion rates 6.4% vs. 0.9% (p = 0.022)., Conclusion: In comparing tubeless with standard PCNL, there was no difference in readmission rates, or significant Clavien complication rates. Patients undergoing tubeless PCNL experienced higher stone-free rates, but more number of patients required postoperative blood transfusion. The decision to leave a nephrostomy tube after PCNL appears unlikely to impact overall complication rates and can be left to surgeon experience and case-based discretion., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Blended psychotherapy (bPT) combines face-to-face psychotherapy with digital interventions to enhance the effectiveness of mental health treatment. The feasibility and effectiveness of bPT have been demonstrated for various mental health issues, although primarily for patients with higher levels of functioning., Objective: This scoping review aims to investigate the feasibility, adherence, and effectiveness of bPT for the treatment of patients with severe mental illnesses (SMIs)., Methods: Following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines, we conducted searches in PubMed, MEDLINE, Embase, PsycINFO, and PsycArticles for studies published until March 23, 2023., Results: Out of 587 screened papers, we incorporated 25 studies encompassing 23 bPT interventions, involving a total of 2554 patients with SMI. The intervention formats and research designs exhibited significant variation. Our findings offer preliminary evidence supporting the feasibility of bPT for SMI, although there is limited research on adherence. Nevertheless, the summarized studies indicated promising attrition rates, spanning from 0% to 37%, implying a potential beneficial impact of bPT on adherence to SMI treatment. The quantity of evidence on the effects of bPT for SMI was limited and challenging to generalize. Among the 15 controlled trials, 4 concluded that bPT interventions were effective compared with controls. However, it is noteworthy that 2 of these studies used the same study population, and the control groups exhibited significant variations., Conclusions: Overall, our review suggests that while bPT appears promising as a treatment method, further research is necessary to establish its effectiveness for SMI. We discuss considerations for clinical implementation, directions, and future research., (©Yamina Ehrt-Schäfer, Milan Rusmir, Johannes Vetter, Erich Seifritz, Mario Müller, Birgit Kleim. Originally published in JMIR Mental Health (https://mental.jmir.org), 26.12.2023.)

Introduction: In 2014, the AUA published guidelines regarding the evaluation of cryptorchidism. This multi-institutional study aims to determine if these guidelines reduced the age of referral and the utilization of ultrasound in boys with cryptorchidism. We hypothesize that delayed referral continues, and utilization of ultrasound remains unchanged., Methods: A retrospective review of boys referred for the evaluation of cryptorchidism was performed at 4 academic institutions, collecting data for 1 year prior (2013) and 2 nonconsecutive years following guideline creation (2015 and 2019). Across these time frames, we compared median ages at evaluation and surgery, and rates of patient comorbidities, orchiopexy, and preevaluation ultrasound., Results: A total of 3,293 patients were included. The median age at initial pediatric urology evaluation in all cohorts was 39 months (IQR: 14-92 months). Following publication of the AUA Guidelines, there was no difference ( P = .08) in the median age at first evaluation by a pediatric urologist between 2013 and 2015, and an increase ( P = .03) between 2013 and 2019. Overall, 21.2% of patients received an ultrasound evaluation prior to referral, with no significant difference between 2013 and 2015 ( P = .9) or 2019 ( P = .5) cohorts., Conclusions: Our data suggest that, despite publication of the AUA Guidelines on evaluation and treatment of cryptorchidism, there has been no reduction in the age of urological evaluation or the utilization of imaging in boys with undescended testis. Finding alternative avenues to disseminate these evidence-based recommendations to referring providers and exploring barriers to guideline adherence is necessary to improve care for patients with cryptorchidism.

Among the toxic metabolites of the fungal world, those that, due to their strong biological effect, can seriously (even fatally) damage the life processes of humans (and certain groups of animals) stand out. Amatoxin-containing mushrooms and the poisonings caused by them stand out from the higher fungi, the mushrooms. There are already historical data and records about such poisonings, but scientific research on the responsible molecules began in the middle of the last century. The goals of this review work are as follows: presentation of the cosmopolitan mushroom species that produce amanitins (which are known from certain genera of four mushroom families), an overview of the chemical structure and specific properties of amanitins, a summary of the analytical methods applicable to them, a presentation of the "medical history" of poisonings, and a summary of the therapeutic methods used so far. The main responsible molecules (the amanitins) are bicyclic octapeptides, whose structure is characterized by an outer loop and an inner loop (bridge). It follows from the unusual properties of amanitins, especially their extreme stability (against heat, the acidic pH of the medium, and their resistance to human, and animal, digestive enzymes), that they are absorbed almost without hindrance and quickly transported to our vital organs. Adding to the problems is that accidental consumption causes no noticeable symptoms for a few hours (or even 24-36 h) after consumption, but the toxins already damage the metabolism of the target organs and the synthesis of nucleic acid and proteins. The biochemical catastrophe of the cells causes irreversible structural changes, which lead to necrotic damage (in the liver and kidneys) and death. The scientific topicality of the review is due to the recent publication of new data on the probable antidote molecule (ICR: indocyanine green) against amanitins. Further research can provide a new foundation for the therapeutic treatment of poisonings, and the toxicological situation, which currently still poses a deadly threat, could even be tamed into a controllable problem. We also draw attention to the review conclusions, as well as the mycological and social tasks related to amanitin poisonings (prevention of poisonings).

Neuromorphic computers emulate the human brain while being extremely power efficient for computing tasks. In fact, they are poised to be critical for energy-efficient computing in the future. Neuromorphic computers are primarily used in spiking neural network-based machine learning applications. However, they are known to be Turing-complete, and in theory can perform all general-purpose computation. One of the biggest bottlenecks in realizing general-purpose computations on neuromorphic computers today is the inability to efficiently encode data on the neuromorphic computers. To fully realize the potential of neuromorphic computers for energy-efficient general-purpose computing, efficient mechanisms must be devised for encoding numbers. Current encoding mechanisms (e.g., binning, rate-based encoding, and time-based encoding) have limited applicability and are not suited for general-purpose computation. In this paper, we present the virtual neuron abstraction as a mechanism for encoding and adding integers and rational numbers by using spiking neural network primitives. We evaluate the performance of the virtual neuron on physical and simulated neuromorphic hardware. We estimate that the virtual neuron could perform an addition operation using just 23 nJ of energy on average with a mixed-signal, memristor-based neuromorphic processor. We also demonstrate the utility of the virtual neuron by using it in some of the μ-recursive functions, which are the building blocks of general-purpose computation., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Nephron-sparing surgery is important in patients with multiple renal tumors, especially if associated with a solitary kidney or hereditary syndrome. Prior studies have shown partial nephrectomy (PN) of multiple ipsilateral renal masses to have good oncologic and renal function outcomes. We aim to compare renal function changes, complications, and warm ischemia time (WIT) of partial nephrectomy of a single renal mass (sPN) vs those of partial nephrectomy of multiple ipsilateral renal masses (mPN). Materials and Methods: We retrospectively reviewed our multi-institutional PN database. We matched robotic sPN and mPN patients ∼3:1 using "nearest neighbor" propensity score matching based on age, Charlson comorbidity index (CCI), total tumor size, and nephrometry score. Univariate analysis was performed, and multivariable models were fit controlling for age, gender, CCI, and tumor size. Results: Fifty mPN and 146 sPN patients were matched. The mean total tumor size was 3.3 and 3.2 cm, respectively ( p  = 0.363). The mean nephrometry score in both groups was 7.3 and 7.2, respectively ( p  = 0.772). Estimated blood loss (EBL) was 137.6 and 117.8 mL, respectively ( p  = 0.184). The mPN group had higher operative time (174.6 vs 156.4 minutes, p  = 0.008) and WIT (17.0 vs 15.3 minutes, p  = 0.032). There was no significant difference in the change in glomerular filtration rate (mPN -6.4% vs sPN -8.7%, p  = 0.712). Complications (Clavien 2+) occurred in 10.2% of mPN and 11.3% of sPN patients ( p  = 0.837). A multivariable linear model predicts a nonstatistically significant difference of 1.4 minutes of additional WIT in the mPN group ( p  = 0.242). There was no statistical difference in complication rates between groups in a multivariable model (odds ratio 1.00, p  = 0.991). Conclusions: Robotic PN in our multi-institutional matched comparison of mPN and sPN showed no difference in complications, renal functional outcomes, or EBL. mPN was associated with increased operative time and WIT, though the WIT difference was not significant on multivariable analysis.

Objective: To determine risk factors and time course for repeat procedures after ureteroscopy (URS) or shockwave lithotripsy (SWL) procedure using a large employer-based claims database., Methods: We identified all patients who underwent treatment for ureteral or renal stone with URS or SWL from January 1, 2007 to December 31, 2014 using the IBM MarketScan Commercial Database. Repeat stone procedure was evaluated after a 90-day grace period from the index procedure. Patients were followed until December 31, 2017. We performed multivariate analyses using Cox proportional hazards to determine independent risk factors for repeat procedure after the initial stone removal., Results: A total of 189,739 patients underwent a SWL or URS and were included in the study. The incidence of repeat procedure per 100 person years was 6.8, and 4.4 after SWL and URS, respectively. The median time to reoperation was 12.5 months for SWL and 14.6 months for URS. On multivariable analysis, SWL was associated with an increased risk of repeat procedure compared to URS. (HR = 1.63). Paralysis, neurogenic bladder and inflammatory bowel disease were also associated with an increased risk of repeat procedure (HR = 1.66, 1.40, and 1.36 respectively) CONCLUSION: In a large national cohort, patients with paralysis and neurogenic bladder had a significantly higher risk of repeat stone procedure. SWL was associated with higher risk of repeat procedure than URS. Urologists can use these data to identify and counsel patients at high risk for need for recurrent procedure., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: To better understand the sensation of bladder "pressure" and "discomfort", and how they are similar or distinct from the "pain" and "urgency" symptoms in IC/BPS and OAB., Methods: IC/BPS and OAB patients rated their bladder pain, pressure, discomfort, and urinary urgency on separate 0-10 numeric rating scales (NRS). Their NRS ratings were compared between IC/BPS and OAB, and Pearson correlations were performed., Results: Among IC/BPS patients (n = 27), their mean numeric ratings of pain, pressure, discomfort, and urinary urgency were almost identical (6.6 ± 2.1, 6.0 ± 2.5, 6.5 ± 2.2, and 6.0 ± 2.8 respectively). The three-way correlations between pain, pressure, or discomfort were very strong (all > 0.77). Among OAB patients (n = 51), their mean numeric ratings of pain, pressure, and discomfort (2.0 ± 2.6, 3.4 ± 2.9, 3.4 ± 2.9) were significantly lower than urgency (6.1 ± 2.6, p < 0.001). The correlations between urgency and pain, and between urgency and pressure were weak in OAB (0.21 and 0.26). The correlation between urgency and discomfort was moderate in OAB (0.45). The most bothersome symptom of IC/BPS was bladder/pubic pain, while the most bothersome symptom of OAB was urinary urgency and daytime frequency., Conclusions: IC/BPS patients interpreted bladder pain, pressure, or discomfort as the similar concepts and rated their intensity similarly. It is unclear whether pressure or discomfort provide additional information beyond pain in IC/BPS. Discomfort may also be confused with urgency in OAB. We should re-examine the descriptors pressure or discomfort in the IC/BPS case definition., (© 2023. The Author(s).)

Spontaneous infiltration of a porous preform by a metallic melt provides the potential of generating metal matrix composites (MMCs) with tailored combinations of material properties at low cost. The bulk of tool inserts for injection molding must sustain high mechanical and thermal loads and simultaneously exhibit high thermal conductivity for efficient temperature control of the mold insert. To fulfill these contradictory requirements, AISI H11 tool steel preforms were infiltrated by liquid copper. The impact of the fine powder fraction (0 wt.% to 15 wt.%) blended to a coarse H11 powder in the preform on thermal conductivity, Vickers hardness and tensile strength was elucidated. The thermal conductivity of the composites could be enhanced by a factor of 1.84 (15 wt.% fine powder) and 2.67 (0 wt.% fine powder) with respect to the sintered H11 tool steel. By adding 15 wt.% fine powder to the coarse host powder, the tensile strength and Vickers hardness of the copper-infiltrated steel were 1066.3 ± 108.7 MPa and 366 ± 24 HV1, respectively, whereas the H11 tool steel yielded 1368.5 ± 89.3 MPa and 403 ± 17 HV1, respectively. Based on the results obtained, an appropriate particle size distribution (PSD) may be selected for preform preparation according with the requirements of a future mold insert., Competing Interests: The authors declare no conflicts of interest.

Carbohydrates, including polysaccharide macromolecules, are the main constituents of the fungal cell wall. Among these, the homo- or heteropolymeric glucan molecules are decisive, as they not only protect fungal cells but also have broad, positive biological effects on the animal and human bodies. In addition to the beneficial nutritional properties of mushrooms (mineral elements, favorable proteins, low fat and energy content, pleasant aroma, and flavor), they have a high glucan content. Folk medicine (especially in the Far East) used medicinal mushrooms based on previous experience. At the end of the 19th century, but mainly since the middle of the 20th century, progressively more scientific information has been published. Glucans from mushrooms are polysaccharides that contain sugar chains, sometimes of only one kind (glucose), sometimes having several monosaccharide units, and they have two (α and β) anomeric forms (isomers). Their molecular weights range from 10 4 to 10 5 Da, and rarely 10 6 Da. X-ray diffraction studies were the first to determine the triple helix configuration of some glucans. It seems that the existence and integrity of the triple helix structure are criteria for their biological effects. Different glucans can be isolated from different mushroom species, and several glucan fractions can be obtained. The biosynthesis of glucans takes place in the cytoplasm, the processes of initiation and then chain extension take place with the help of the glucan synthase enzyme complex (EC 2.4.1.34), and the sugar units are provided by sugar donor UDPG molecules. The two methods used today for glucan determination are the enzymatic and Congo red methods. True comparisons can only be made using the same method. Congo red dye reacts with the tertiary triple helix structure, and the resulting glucan content better reflects the biological value of glucan molecules. The biological effect of β-glucan molecules is proportional to the integrity of the tertiary structure. The glucan contents of the stipe exceed the values of the caps. The glucan levels of individual fungal taxa (including varieties) differ quantitatively and qualitatively. This review presents in more detail the glucans of lentinan (from Lentinula edodes ), pleuran (from Pleurotus ostreatus ), grifolan (from Grifola frondose ), schizophyllan (from Schizophyllum commune ), and krestin (from Trametes versicolor ), along with their main biological effects.

Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by altered myeloid progenitor cell proliferation and differentiation. As in many other cancers, epigenetic transcriptional repressors such as histone deacetylases (HDACs) are dysregulated in AML. Here, we investigated (1) HDAC gene expression in AML patients and in different AML cell lines and (2) the effect of treating AML cells with the specific class IIA HDAC inhibitor TMP269, by applying proteomic and comparative bioinformatic analyses. We also analyzed cell proliferation, apoptosis, and the cell-killing capacities of TMP269 in combination with venetoclax compared to azacitidine plus venetoclax, by flow cytometry. Our results demonstrate significantly overexpressed class I and class II HDAC genes in AML patients, a phenotype which is conserved in AML cell lines. In AML MOLM-13 cells, TMP269 treatment downregulated a set of ribosomal proteins which are overexpressed in AML patients at the transcriptional level. TMP269 showed anti-proliferative effects and induced additive apoptotic effects in combination with venetoclax. We conclude that TMP269 exerts anti-leukemic activity when combined with venetoclax and has potential as a therapeutic drug in AML.

Robotic assisted laparoscopic prostatectomy (RALP) has become the primary surgical modality in the treatment of prostate cancer. Most patients are discharged on postoperative day one. Same-day discharge is emerging as a potential new standard. We sought to establish factors correlating with post-operative pain after RALP procedures to design a same-day discharge protocol. We retrospectively reviewed 150 of recently performed RALP procedures from March 2020 to January 2021. Patient demographics and intra-operative variables were compared to Numeric Rating Scale (NRS) pain scores and total morphine milliequivalents (MME) at 2 h, 8 h, and averaged over the patient's admission post-operatively or first 48 h, whichever occurred first. We performed univariable and multivariable logistic regression to assess correlations with postoperative pain and narcotic use. NRS average > 3 or any MME given at 2 h postoperatively was significantly associated with continued post-operative pain averaged over admission (r s = 0.32, 0.38, respectively; p < 0.001). MME given was also associated with longer operative time and negative related to body mass index. No other demographic data or intraoperative variables such as diabetes or pneumoperitoneum pressure were correlated with worsened post-operative pain scores > 3 or narcotic use. Local bupivacaine dose was also not associated with improved post-operative pain scores or narcotic use at 8 h (p = 0.98, 0.13). These findings suggest that patients with adequate postoperative pain control at 2 hours may be discharged same day from a pain control perspective. Further clinical evaluation regarding the role of local anesthetic use in RALPs is warranted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Cultivated mushrooms are not only valuable foods of our age (functional foods) but contain certain beneficial chemical components (high level of K and P, very low content of Na, considerable quantities of some microelements, high and valuable protein but low fat contents). Some cultivated mushrooms have anti-carcinogenic effects caused first of all by polysaccharides (Lentinan: Lentinula edodes) and by triterpenoids (ganoderic acids: Ganoderma lucidum or unsaturated fatty acids: linoleic, linolenic acids); antidiabetic effects, which can improve the sugar metabolism of patients (Coprinus comatus, Ganoderma lucidum, Agaricus bisporus); anti-microbial effects, caused partly by smaller triterpenoids or by higher molecules, i.e. by direct or indirect effects: via stimulation of the immune system. Certain mushrooms have antioxidant effects, provided mostly by higher radical scavenging activity of phenolic (flavonoid) components. The chemical composition and its biological effects form together the biological values of the cultivated mushrooms. The following review would like to summarize the most important facts of this topic. [ABSTRACT FROM AUTHOR]

Previous studies related to the ptaquiloside molecule, a carcinogenic secondary metabolite known from the world of ferns, are summarised. Ptaquiloside (PTA) belongs to the group of norsesquiterpenes of the illudane type. The name illudane refers to the fungal taxa from which the first representatives of the molecular group were identified. Ptaquiloside occurs mainly in Pteridium fern species, although it is also known in other fern taxa. The species of the genus Pteridium are common, frequent invasive species on all continents, and PTA is formed in smaller or larger amounts in all organs of the affected species. The effects of PTA and of their derivatives on animals and humans are of great toxicological significance. Its basic chemical property is that the molecule can be transformed. First, with the loss of sugar moiety, ptaquilosine is formed, and then, under certain conditions, a dienone derivative (pteridienone) may arise. The latter can alkylate (through its cyclopropane groups) certain molecules, including DNA, in animal or human organisms. In this case, DNA adducts are formed, which can later have a carcinogenic effect through point mutations. The scope of the PTA is interdisciplinary in nature since, for example, molecules from plant biomass can enter the body of animals or humans in several ways (directly and indirectly). Due to its physico-chemical properties (excellent water solubility), PTA can get from the plant into the soil and then into different water layers. PTA molecules that enter the soil, but mainly water, undergo degradation (hydrolytic) processes, so it is very important to clarify the toxicological conditions of a given ecosystem and to estimate the possible risks caused by PTA. The toxicoses and diseases of the animal world (mainly for ruminant farm animals) caused by PTA are briefly described. The intake of PTA-containing plants as a feed source causes not only various syndromes but can also enter the milk (and meat) of animals. In connection with the toxicological safety of the food chain, it is important to investigate the transport of carcinogenic PTA metabolites between organisms in a reassuring manner and in detail. This is a global, interdisciplinary task. The present review aims to contribute to this.

Rotavirus (RV) viroplasms are cytosolic inclusions where both virus genome replication and primary steps of virus progeny assembly take place. A stabilized microtubule cytoskeleton and lipid droplets are required for the viroplasm formation, which involves several virus proteins. The viral spike protein VP4 has not previously been shown to have a direct role in viroplasm formation. However, it is involved with virus-cell attachment, endocytic internalization, and virion morphogenesis. Moreover, VP4 interacts with actin cytoskeleton components, mainly in processes involving virus entrance and egress, and thereby may have an indirect role in viroplasm formation. In this study, we used reverse genetics to construct a recombinant RV, rRV/VP4-BAP, that contains a biotin acceptor peptide (BAP) in the K145-G150 loop of the VP4 lectin domain, permitting live monitoring. The recombinant virus was replication competent but showed a reduced fitness. We demonstrate that rRV/VP4-BAP infection, as opposed to rRV/wt infection, did not lead to a reorganized actin cytoskeleton as viroplasms formed were insensitive to drugs that depolymerize actin and inhibit myosin. Moreover, wild-type (wt) VP4, but not VP4-BAP, appeared to associate with actin filaments. Similarly, VP4 in coexpression with NSP5 and NSP2 induced a significant increase in the number of viroplasm-like structures. Interestingly, a small peptide mimicking loop K145-G150 rescued the phenotype of rRV/VP4-BAP by increasing its ability to form viroplasms and hence improve virus progeny formation. Collectively, these results provide a direct link between VP4 and the actin cytoskeleton to catalyze viroplasm assembly. IMPORTANCE The spike protein VP4 participates in diverse steps of the rotavirus (RV) life cycle, including virus-cell attachment, internalization, modulation of endocytosis, virion morphogenesis, and virus egress. Using reverse genetics, we constructed for the first time a recombinant RV, rRV/VP4-BAP, harboring a heterologous peptide in the lectin domain (loop K145-G150) of VP4. The rRV/VP4-BAP was replication competent but with reduced fitness due to a defect in the ability to reorganize the actin cytoskeleton, which affected the efficiency of viroplasm assembly. This defect was rescued by adding a permeable small-peptide mimicking the wild-type VP4 loop K145-G150. In addition to revealing a new role of VP4, our findings suggest that rRV harboring an engineered VP4 could be used as a new dual vaccination platform providing immunity against RV and additional heterologous antigens.

Background: Coronary revascularization is recommended to treat ischemic cardiomyopathy. However, the relations of revascularization-associated ejection fraction (EF) change to subsequent outcomes have not been elucidated., Methods: In 10 071 veterans (mean age 67 years; 1% women; 15% non-White) who underwent a first percutaneous coronary intervention (PCI) or coronary artery bypass grafting between January 1, 1995, and December 31, 2010, and had prerevascularization and postrevascularization EF measured, we calculated delta-EF (postprocedure EF-preprocedure EF). We related delta-EF as a continuous measure and as categories (≤-5, -5

Background: Next-generation sequencing (NGS) is nowadays the most used high-throughput technology for DNA sequencing. Among others NGS enables the in-depth analysis of immune repertoires. Research in the field of T cell receptor (TCR) and immunoglobulin (IG) repertoires aids in understanding immunological diseases. A main objective is the analysis of the V(D)J recombination defining the structure and specificity of the immune repertoire. Accurate processing, evaluation and visualization of immune repertoire NGS data is important for better understanding immune responses and immunological behavior., Results: ImmunoDataAnalyzer (IMDA) is a pipeline we have developed for automatizing the analysis of immunological NGS data. IMDA unites the functionality from carefully selected immune repertoire analysis software tools and covers the whole spectrum from initial quality control up to the comparison of multiple immune repertoires. It provides methods for automated pre-processing of barcoded and UMI tagged immune repertoire NGS data, facilitates the assembly of clonotypes and calculates key figures for describing the immune repertoire. These include commonly used clonality and diversity measures, as well as indicators for V(D)J gene segment usage and between sample similarity. IMDA reports all relevant information in a compact summary containing visualizations, calculations, and sample details, all of which serve for a more detailed overview. IMDA further generates an output file including key figures for all samples, designed to serve as input for machine learning frameworks to find models for differentiating between specific traits of samples., Conclusions: IMDA constructs TCR and IG repertoire data from raw NGS reads and facilitates descriptive data analysis and comparison of immune repertoires. The IMDA workflow focus on quality control and ease of use for non-computer scientists. The provided output directly facilitates the interpretation of input data and includes information about clonality, diversity, clonotype overlap as well as similarity, and V(D)J gene segment usage. IMDA further supports the detection of sample swaps and cross-sample contamination that potentially occurred during sample preparation. In summary, IMDA reduces the effort usually required for immune repertoire data analysis by providing an automated workflow for processing raw NGS data into immune repertoires and subsequent analysis. The implementation is open-source and available on https://bioinformatics.fh-hagenberg.at/immunoanalyzer/ ., (© 2021. The Author(s).)

Objective: To evaluate if decreasing postop abx prophylaxis affects UTI and wound infection rates in patients following urethroplasty., Methods: A retrospective review of patients who underwent urethroplasty from 9/2017 - 3/2020 by a single surgeon was performed. All patients received urine culture specific perioperative IV abx prior to urethroplasty and kept a urethral catheter for 3 weeks postop. Patients undergoing a urethroplasty from 9/2017 to 12/2018 received extended postop abx prophylaxis for 3 weeks until catheter removal (Group 1). Patients from 12/2018 to 3/2020 received abx for 3 days around catheter removal (Group 2). UTIs, abx complications, and wound infections between groups were evaluated. UTIs were defined as a positive urine culture or reported lower urinary tract symptoms/fevers treated with empiric abx., Results: 120 patients underwent urethroplasty. Group 1 consisted of 60 patients with mean age of 51.9 years and mean stricture length of 3.6 cm. Group 2 had 60 patients with mean age of 53.1 years and mean stricture length of 3.8 cm. 10 patients had UTIs after urethroplasty. There was no significant difference in UTI (6.7% vs 11.7%; P = 0.529) or wound infection rates (3.3% vs 1.7%;' P = 1.000) between the two groups., Conclusion: Extended postoperative antibiotic prophylaxis does not appear to significantly affect UTI or wound infection rates following urethroplasty. The retrospective nature of the study has limitations, however, this is the first comparison of two different antibiotic administration protocols to our knowledge., (Copyright © 2021 Elsevier Inc. All rights reserved.)