Background: The hemodynamics of most prosthetic valves are often inferior to that of the normal native valve, and a significant proportion of patients undergoing surgical (SAVR) or transcatheter aortic valve replacement (TAVR) have high residual transaortic pressure gradients due to prosthesis–patient mismatch (PPM). Since the experience with TAVR has increased and long-term outcomes are reported, a close look at the PPM literature is required in light of new evidence. Methods: For this review, we searched the Embase, Medline, and Cochrane databases from 2000 to 2022. Articles reporting PPM as an outcome following aortic valve replacements were identified and reviewed. Results: The impact of PPM on clinical outcomes aortic valve replacement has not been clear since multiple studies failed to report PPM incidence. However, the PPM after SAVR vary greater than after TAVR, ranging from 8% to almost 80% in SAVR and from 24%-35% in TAVR. Incidence of severe PPM following redo SAVR is ranging from 2 to 9% and following valve-in-valve TAVR is from 14 to 33%, however, while PPM is higher in valve-in-valve TAVR, patients had better survival rates. Conclusions: The gap between valve performance and clinical outcomes in TAVR and SAVR could be reduced by carefully selecting patients for either treatment option. Understanding predictors of PPM can add to the safety, effectiveness, and increased survival benefit of both TAVR and SAVR.

The Vasoactive-Inotropic Score at 48 hours is a good surrogate marker for adverse postoperative events in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass and is limited by its ability to delineate the underlying cause for an unfavourable clinical course. Thus, other predictors such as the Technical Performance Score are likely to highlight the underlying cause and can be used to improve outcomes. However, patients with a high postoperative VIS score at 48 hours may benefit from closer longer-term follow for outcomes such as late survival, functional class, and need for reoperation.

Background: The most worrisome complications in patients supported by left ventricular assist device (LVAD) are pump thrombosis, embolism, and bleeding. The actual rate of these events in patients with sickle-cell disease (SCD) has not well investigated. The aim of our study is to evaluate the outcomes of LVAD implantation in patients with sickle-cell hemoglobinopathy at our institution. Methods: This retrospective, observational, single-center study was conducted on patients with sickle-cell trait (SCT), who underwent LVAD implantation using the HeartMate3 LVAD. Results: LVAD devices were implanted in four patients with SCT. All procedures were performed successfully. All patients had uneventful post-implant course. Overall, the mean follow-up time was 25 months (range 21-28 months) and showed an unremarkable post-implant course. There was a significant improvement in hematological markers over the follow-up period. Conclusions: Despite the limited numbers of patients enrolled in this study, our findings indicate that LVAD surgery is safe in SCD patients and offers remarkable clinical improvement. Further studies are needed to provide more evidence regarding this type of patients undergoing LVAD implantation.

A new approach is proposed to analysis the non-Gaussian random vibration of hyperbolic tangential package. Firstly, the non-Gaussian vibration noise of specified mean, variance, skewness and kurtosis is developed by Hermite polynomial, and verified by Gaussian mixture model (GMM) theory. Secondly, next to analyzing an analytical and numerical response of the two degrees of freedom (TDOF) linear package, the acceleration response of the TDOF hyperbolic tangential package system (HTPS) under non-Gaussian vibration excitation is obtained though the Hermite polynomial and Runge-Kutta method, and the effects of the external excitation and system parameters are investigated. Finally, on the basis of the first-passage probability of the acceleration response, the reliability analysis method is introduced. The analysis provides a guidance to the vibration reliability analysis and packaging optimization design.

A theorem on the maximum regularity of solutions of the nonlinear Sturm-Liouville equation with greatly growing and rapidly oscillating potential in the space $L_2(R)\,(R=(-\infty,\infty))$ is proved in this paper. Two-sided estimates of the Kolmogorov widths of the sets associated with solutions of the nonlinear Sturm-Liouville equation are also obtained. As is known, the obtained estimates given the opportunity to choose approximation apparatus that guarantees the maximum possible error.

Motivated by important applications in materials science and biology, we consider a non-stationary coagulation equation with in-flux and out-flux of particles (cargo). An exact analytical solution to this integrodifferential equation is found in a parametric form. This solution behaves as a decaying exponent with respect to the particle volume (fluorescence intensity in the case of coagulation of endosomes). We demonstrate that our exact solution substantially depends on coagulation kernels (fusion and fission rates) as well as the in-flux and out-flux processes of cargo.

Objective: To investigate the compatibility of oxytocin and tranexamic acid injection products when mixed for the purpose of co-administration by intravenous infusion. Population or Sample: Oxytocin and tranexamic acid were collected from hospitals taking part in a multicentre postpartum haemorrhage treatment (E-MOTIVE) trial in Kenya, Nigeria, Tanzania, and South Africa. Methods: The compatibility of two sentinel products of oxytocin injection and tranexamic acid injection in 200mL infusion bags of both 0.9%w/v saline and Ringer’s Lactate was assessed. We analysed all tranexamic acid -oxytocin combinations, and each evaluation was conducted for up to 6hrs. Subsequently, the compatibility of multiple tranexamic acid products with reference oxytocins products when mixed in 0.9%w/v saline over a period of 1 hour was investigated. Results: We found a significant interaction between certain oxytocin and tranexamic acid products after mixing them in vitro and observing for 1 hour. The interaction substantially impacted oxytocin content leading to reduction in concentration (14.8% - 29.0%) immediately on mixing (t=0 minutes). In some combinations, the concentration continued to decline throughout the stability assessment period. Oxytocin loss was observed in 7 out of 22 (32%) combinations tested. Conclusions: In a clinical setting, mixing oxytocin and tranexamic acid may result in an underdosing of oxytocin, compromising care in an emergency life-threatening situation. The mixing of oxytocin and tranexamic acid injection products for co-administration with IV infusion fluids should be avoided until the exact nature of the interaction and its implications are understood.

The effect of antenatal depressive and anxious symptoms on the rate of physiological birthsA comment on the recently published article by Hulsbosch et al:Association between high levels of comorbid anxiety and depressive symptoms and decreased likelihood of birth without intervention: A longitudinal prospective cohort study

Hemorrhagic cystitis is a common complication following the use of cyclophosphamide. Associated dysuria can be painful and there are few good options to relive pain. Phenazopyridine has historically been utilized for dysuria and is available over the counter. However, it is associated with hematologic side effects with prolonged use.

An accurate medication history prevents medication errors during transitions of care, whereas an inaccurate medication history may lead to unnecessary tests or prolonged hospitalization. We describe the case of a patient with chronic hypothyroidism who presented to the hospital with severe hypothyroidism and reported strict adherence to her home levothyroxine.

Acute Lymphoblastic Leukemia of the Central Nervous System Presenting with Rapid Weight GainConnor P. Hall1 and Alan D. Friedman11Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USACorrespondence: Alan D. Friedman, MDJohns Hopkins UniversityCRB I, Rm. 253 1650 Orleans St. Baltimore, Maryland 21231 Phone: 410-955-2095; Fax: 410-955-8897 Email: [email protected] Count: 863Number of Figures: 1Running Title: Rapid Weight Gain in ALLKey Words: acute lymphoblastic leukemia/ relapse/ weight gain/ central nervous systemAbbreviations:

Wolves (Canis lupus) can exert top-down pressure and shape ecological communities through selective predation of ungulates and beavers (Castor Canadensis). Considering their ability to shape communities through predation, understanding wolf foraging decisions is critical to predicting their ecosystem level effects. Specifically, if wolves are optimal foragers, consumers that optimize tradeoffs between cost and benefits of prey acquisition, changes in these factors may lead to prey switching or negative-density dependent selection with potential consequences for community stability. For wolves, factors affecting cost and benefits include prey vulnerability, risk, reward, and availability which can vary temporally. We described wolf diet in by frequency of occurrence and percent biomass and characterized diet in relation to optimal foraging using prey remains found in wolf scats on Isle Royale National Park, Michigan, USA during May–October 2019–2020. We used logistic regression to estimate prey consumption over time. We predicted prey with temporal variation in cost (vulnerability and/or availability) such as adult and calf moose (Alces alces) and beaver to vary in wolves’ diet. We analyzed 206 scats and identified 62% of remains as beaver, 26% as and moose, and 12% as other (birds, smaller mammals, and wolves). Adult moose were more likely to occur in wolf scat in May, when moose are in poor condition following winter. Similarly, the occurrence of moose calves peaked June–mid July following parturition but before their vulnerability declined as they matured. In contrast, beaver occurrence in wolf scat did not change over time, possibly reflecting the importance of low handling cost prey items for recently introduced lone or paired wolves. Our results demonstrate that wolf diet is plastic and responsive to temporal changes in prey acquisition cost as predicted by optimal foraging theory. Temporal fluctuation in diet may influence wolves’ ecological role if prey respond to increased predation risk by altering their foraging or breeding behavior.

The objective of the study was to simulate New Zealand’s foot-and-mouth disease (FMD) operational plan to determine personnel requirements for a FMD response and understand how the numbers of frontline staff available could affect the size and duration of FMD outbreaks, when using stamping-out (SO) measures with or without vaccination. The model utilized a national dataset of all known livestock farms. Each simulation randomly seeded infection into a single farm. Transmission mechanisms included direct and indirect contacts, local and airborne spread. Prior to each simulation, the numbers of personnel for front-line tasks were set randomly. In a random subset of simulations, vaccination was allowed to be deployed as an adjunct to SO. Front-line tasks included contact tracing, surveillance of at-risk farms, depopulation and vaccination using teams comprising personnel of the different types required by New Zealand’s operational plans. The effect of personnel numbers on the size and duration of epidemics were explored using machine learning methods. In the second stage of the study, using a subset of iterations where numbers of personnel were unconstrained, the number of personnel used each day were quantified. When personnel resources were unconstrained, the 95 th percentile and maximum number of infected places (IPs) were 78 and 462 respectively, and the 95 th percentile and maximum duration were 69 and 217 days respectively. However, severe constraints on personnel resources allowed some outbreaks to exceed the size of the UK 2001 FMD epidemic which had 2026 IPs. The number of veterinarians available had a major influence on the size and duration of outbreaks, while the availability of other personnel types did not. A shortage of veterinarians was associated with an increase in time to detect and depopulate IPs, allowing for continued transmission. Emergency vaccination placed a short-term demand for additional staff at the start of the vaccination programme, but the overall number of person days used were similar to SO-only strategies. This study determined the optimal numbers of front-line personnel required to implement the current operational plans to support an FMD response in New Zealand. A shortage of veterinarians was identified as the most influential factor to impact disease control outcomes. Emergency vaccination led to earlier control of an FMD outbreak, but also resulted in a short-term spike in demand for personnel. A successful response needs to have access to sufficient personnel, particularly veterinarians, trained in response roles and available at short notice.

Objectives: New temperature management concepts of moderate and mild hypothermic circulatory arrest during aortic arch surgery have gained weight over profound cooling. Comparisons of all temperature levels have rarely been performed. We performed direct and indirect comparisons of deep hypothermic circulatory arrest (DHCA) (≤20°C), moderate hypothermic circulatory arrest (MHCA) (20.1°C to 25°C), and mild hypothermic circulatory arrest (mild HCA) (≥25.1°C) in a network meta-analysis. Methods: The literature was systematically searched for all papers published through February 2022 reporting on clinical outcomes after aortic arch surgery utilizing DHCA, MHCA and mild HCA. The primary outcome was operative morality. The secondary outcomes were postoperative stroke and acute kidney failure (AKI). Results: A total of 34 studies were included, with a total of 12 370 patients. DHCA was associated with significantly higher postoperative incidence of stroke when compared with MHCA (odds ratio (OR), 1.46, 95% (confidence interval) CI, 1.19-1.78) and mild HCA: (OR, 1.50, 95% CI, 1.14-1.98). Furthermore, DHCA and MHCA were associated with higher operative mortality when compared with mild HCA (OR 1.71, 95% CI, 1.23-2.39 and OR 1.50, 95% CI, 1.12-2.00, respectively). Separate analysis of randomized and propensity score matched studies showed sustained increased risk of stroke with DHCA in contrast to MHCA and mild HCA (OR, 1.61, 95% CI, 1.18-2.20, P-value = 0.0029 and OR, 1.74, 95% CI, 1.09-2.77, P-value = 0.019). Conclusions: In the included studies, the moderate to mild hypothermia strategies were associated with decreased operative mortality and the risk of postoperative stroke. Large-scale prospective studies are warranted to further explore appropriate temperature management for the treatment of aortic arch pathologies.

Over the last two decades, there has been a huge increase in our understanding of microbial diversity, structure and composition enabled by high throughput sequencing (HTS) technologies. Yet, it is unclear how the number of sequences translates to the number of cells or species within the community. Additional observational data may be required to ensure relative abundance patterns from sequence reads are biologically meaningful or presence absence data may be used instead of abundance. The goal is to obtain robust community abundance data, simultaneously, from environmental samples. In this issue of Molecular Ecology Resources, Karlusich et al., (2022) describe a new method for quantifying phytoplankton cell abundance. Using Tara Oceans datasets, the authors propose the photosynthetic gene psbO for reporting accurate relative abundance of the entire phytoplankton community from metagenomic data. The authors demonstrate improved correlations with traditional optical methods including microscopy and flow cytometry, improving upon current molecular identification typically using rRNA markers genes. Furthermore, to facilitate application of their approach, the authors curated a psbO gene database for accessible taxonomic queries. This is an important step towards improving species abundance estimates from molecular data and eventually reporting of absolute species abundance, enhancing our understanding of community dynamics.

Pena-Shokeir Syndrome is considered to be a fatal congenital condition that is rarely diagnosed in neonates. We present the first ever reported case of Pena-Shokeir Syndrome from Syria. Both clinical assessment and early prenatal diagnosis are necessary to give more realistic options for the mother and the baby.

Pain can be a challenging complication experienced by patients who have Guillain- Barré Syndrome(GBS). Managing pain can be difficult and may require the use of multiple agents and still may not treat pain. This case report describes the use of an epidural to manage pain in a patient with GBS.

Background and Purpose: ISX9 is a neurogenesis-promoting small molecule compound which can upregulate the expression of NeuroD1 and induce differentiation of neuronal, cardiac and islet endocrine progenitors. So far, the molecular mechanisms underlying the action of ISX9 still remain elusive. Experimental Approach: To identify a novel agonist of the Wnt/β‐catenin, a cell-based SuperTOPFlash reporter system was used to screen known-compound libraries. An activation effect of ISX9 on the Wnt/β‐catenin pathway was analysed with the SuperTOPFlash or SuperFOPFlash reporter system. Effects of ISX9 on Axin1/LRP6 interaction were examined using a mammalian two-hybrid system, co‐immunoprecipitation, microscale thermophoresis (MST), emission spectra and mass spectroscopy assays. The expression of Wnt target and stemmness marker genes were evaluated with real‐time PCR and immunoblotting. In vivo hair regeneration abilities of ISX9 were analysed by immunohistochemical staining, real‐time PCR and immunoblotting in hair regrowth model using C57BL/6J mice. Key Results: In this study, ISX9 was identified as a novel agonist of the Wnt/β‐catenin pathway. ISX9 targeted Axin1 by covalently binding to its N-terminal region and potentiated the LRP6-Axin1 interaction, thereby resulting in the stabilization of β‐catenin and upregulation of Wnt target genes and stemmness marker genes. Moreover, the topical application of ISX9 markedly promoted hair regrowth in C57BL/6J mice and induced hair follicle transition from telogen to anagen via enhancing Wnt/β‐catenin pathway. Conclusions and Implications: Taken together, our study unraveled that ISX9 could activate Wnt/β‐catenin signaling by potentiating the association between LRP6 and Axin1, and may be a promising therapeutic agent for alopecia treatment