Comment On: Sarcopenia is a Prognostic Outcome Marker in Children with High-Risk Hepatoblastoma

Maternal diabetes insipidus does not usually adversely affect the course of pregnancy. We present a rare case of central diabetes insipidus diagnosed at 31 weeks of gestation with fetal oligohydramnios successfully treated with intranasal desmopressin. To date, only three cases of diabetes insipidus with oligohydramnios have been reported.

Aim To undertake a scoping review of pharmacists’ activities in opioid medicines management in primary care settings, including those developed or led by pharmacists, or in which pharmacists were members of broader multi-disciplinary teams; and to collate the activities, models of care and settings, and reported outcomes. Methods The bibliographic databases MEDLINE, EMBASE, International Pharmaceutical Abstracts, CINAHL, SCOPUS and Web of Science were searched. Studies with quantitative evaluation and published in English were eligible. Participants were patients with any pain category or an opioid use disorder, and healthcare providers. Studies originating in hospitals or involving supply functions were not included. Screening of literature and data charting of results were undertaken by two researchers. Results The 47 studies included in the scooping review occurred in primary care settings collated into four categories: general practice or primary care clinics; healthcare organisations; community pharmacies and outreach services. Studies were primarily of opioid use in chronic, non-cancer pain. Other indications were opioid use disorder, cancer and dental pain. Pharmacist activities targeted risk-mitigation, patient and provider education and broader, strategic approaches. Patient-related outcomes included reduced opioid load, improved functionality and symptom management, enhanced access to services and medication-assisted treatments, and engagement in risk-mitigation strategies. Behaviour change of providers was demonstrated. Conclusion The review has identified the significant contribution that pharmacists working in primary care settings can make to minimise harm from opioids. Strategies implemented in isolation have the potential to further reduce adverse clinical outcomes with greater collaboration and coordination, such as opioid stewardship.

Despite the potential of tissue engineering approaches for cartilage repair, a major shortcoming is the low biosynthetic response of chondrocytes. While different strategies have been investigated to upregulate tissue formation, a novel approach may be to control nutrient metabolism. Although known for their anaerobic metabolism of glucose, chondrocytes are more synthetically active when cultured under conditions that elicit mixed aerobic-anaerobic metabolism. Here, we postulate this metabolic switch induces hypoxia inducible factor 1α (HIF-1α) signaling leading to improved tissue growth. Transition to different metabolic states can result in the pooling of intracellular metabolites, several of which can stabilize HIF-1α by interfering with proline-hydroxylase-2 (PHD2). Chondrocytes cultured under increased media availability accelerated tissue deposition (2.2 to 3.5-fold) with the greatest effect occurring at intermediate volumes (2 mL/106 cells). Under higher media volumes, metabolism switched from anaerobic to mixed aerobic-anaerobic. At and beyond this transition, maximal changes in PHD2 activity (- 45%), HIF-1α protein expression (8-fold increase), and HIF-1 gene target expression were observed (2.0 to 2.7-fold increase). Loss-of-function studies using YC-1 (to degrade HIF-1α) confirmed the involvement of HIF-1 signaling under these conditions. Lastly, targeted metabolomic studies of glucose metabolites (14 in total) revealed that both intracellular lactate and succinate correlated with PHD2 activity. Although both metabolites can inhibit PHD2, this effect can most likely be attributed to lactate as succinate was only present in trace amounts. However, addition work (e.g., 13C flux analyses) are required to confirm this assertion. Nevertheless, by harnessing this newly identified metabolic switch, functional engineered cartilage implants may be developed without the need for sophisticated methods which would allow for improved translation into the clinical realm.

In this paper, the anti-plane shear motion of an asymmetric three-layered inhomogeneous elastic plate has been examined. An asymptotic approach is employed for the present investigation. Both the generalized and unified dispersion relations within the long-wave low-frequency range have been determined. The obtained unified dispersion relation is investigated taking into account the recently analyzed material contrast for layered plate with mixed stiff-soft layers of different material properties. Finally, we make comparison with symmetric plate being a special case of the asymmetric plate under consideration in the end.

Rituximab use in multiple sclerosis has been promising. Cytokine release syndrome (CRS) is a common side effect of rituximab in patients with lymphoma. We report a case of a 44-year-old man with a history of relapsing-remitting multiple sclerosis, who presented with signs and symptoms consistent with CRS after rituximab initiation.

In silico search for planar hexacoordinate silicon center has been initiated by global minimum screening with density functional theory and energy refinement using coupled cluster theory. The search resulted in a local minimum of SiAl3Mg3H2+ structure which contains a planar hexacoordinate silicon center (phSi). The phSi structure is 5.8 kcal/mol higher in energy than the global minimum. However, kinetic studies reveal that the local minimum structure has enough stability to be detected experimentally. Born-Oppenheimer molecular dynamics (BOMD) simulations reveal that the phSi structure can be maintained up to 400 K. The formation of multiple bonds between the central silicon atom and framework aluminium atom is the key stabilizing factor for the planar structure.

An 83 year old female had asymptomatic SARS-CoV-2 infection while taking ruxolitinib. She remained RT-PCR positive for viral RNA for >120 days, Pegylated interferon for 4 weeks led to viral RNA clearance. The observations support combination therapy of ruxolitinib + interferon for COVID-19.

Germline mutations are the raw material for natural selection, driving species evolution and the creation of earth’s biodiversity. Life on earth would stagnate without this driver of genetic diversity. Yet, it is a double-edged sword. An excess of mutations can have devastating effects on fitness and population viability. It is therefore one of the great challenges of molecular ecology to determine the rate and spectrum by which these mutations accrue across the tree of life. Advances in high-throughput sequencing are providing new opportunities for characterizing these rates and patterns within species and populations, thus informing essential evolutionary parameters such as the timing of speciation events, the intricacies of historical demography, and the degree to which lineages are subject to the burdens of mutational load. Here, we will focus on the applications and limitations of whole-genome comparisons among closely related individuals in what are typically described as “trio” analyses for the detection of germline mutations as they arise in real time. By sequencing and comparing whole-genomes generated for individuals of known relatedness – typically, parent to offspring – investigators can ideally count and characterize mutations as they appear per generation. The promise for gaining insight into classic hypotheses of molecular evolution is high, though so too is the cost. Namely, the technical challenges are daunting given that pedigree-based studies are essentially searching for needles in a haystack. Even so, the opportunities are so enticing, and the field so young, we can say with confidence that fundamental insights have only just begun to emerge.

Commentary:

Background and Purpose: Individualized assessment of the activity of cytochrome P450 2D6 (CYP2D6), a highly variable drug-metabolizing enzyme, is performed through phenotyping during which a probe drug is administered to measure the enzyme’s activity. In order to avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe drug, the development of non-invasive tools for real-time phenotyping of CYP2D6 could significantly contribute to the expansion of precision medicine in clinical practice. This study focuses on the identification of endogenous markers of the CYP2D6 enzyme in human biofluids using a liquid chromatography (LC)-high-resolution mass spectrometry (HRMS)-based metabolomics approach. Experimental Approach: Data from a control session were compared to data from an inhibition session. Before the latter, healthy volunteers (extensive and ultrarapid metabolizers) received a daily dose of paroxetine 20 mg over seven days. CYP2D6 genotyping and phenotyping, using single oral dose of dextromethorphan 5 mg, were also performed in all participants. Key Results: In CYP2D6 extensive and ultrarapid metabolizers (n = 37), mean relative intensities of five features were significantly reduced during the inhibition session compared to the control session (fold changes ≤ 0.67, FDR-adjusted P < 0.0001). Furthermore, mean relative intensities of these candidates were significantly higher in the CYP2D6 extensive-ultrarapid metabolizer group (n = 37) compared to the poor metabolizer group (n = 6) (fold changes ≤ 0.67, P < 0.0001). Conclusion and Implications: The applied untargeted metabolomics strategy was able to identify five CYP2D6 endogenous metabolites, a promising discovery for non-invasive phenotyping and personalised medicine.

Objective: To present an alternative surgical technique in treating cases of Chiari I Malformation with mild-to-moderate syringomyelia after decompressive suboccipital craniectomy: incising only the outer layer of the dura mater, then dissecting it from the inner layer without opening the latter. Methods and Results: We utilized this technique in a short series of three cases who were admitted in our department for mild symptoms such as intermittent headache and dissociated sensory loss in the upper limbs, caused by a Chiari Malformation Type I. The patients were placed in the sitting position. We performed a reduced median suboccipital craniectomy and resection of the posterior arch of C1 adapted to the level of tonsil descent, from a limited superior half to a complete resection. Afterwards, we incised the outer dural layer, while sparing the inner one. Using a fine dissector, we then split apart the outer and inner layers to the margin of the craniectomy. Through the transparency of the inner layer and the arachnoid, the cerebellum and the medulla were visible and pulsating. An autologous fascia duraplasty was then performed. The postoperative course was favorable in all cases, patients being discharged without any deficits and with complete symptom resolution. Conclusions: Interlayer dural split technique can be used effectively in treating symptomatic cases of type I Chiari malformation in adults, with mild-to-moderate syringomyelia. It is less invasive than opening the dura and possibly more effective than decompressive craniectomy and C1 laminectomy alone. This technique must be validated in a larger case-control series.

Objective: This study aimed to investigate the association between carotid intima-media changes that play a part in the atherosclerotic process in childhood obesity and fibrin monomers as an important indicator of fibrin plaque. Methods: This is a cross-sectional study of obese children and non-obese healthy control subjects. Height, weight, body mass index, waist/hip ratio, systolic/diastolic blood pressures were recorded, in addition, biochemistry, hemogram, fibrin monomers and d-dimer were measured in both groups. Right and left common carotid intima-media thicknesses were measured by ultrasonography and mean carotid intima-media thickness was calculated. Results: Obese children (n=89, 46.1% girls, median age: 12.6±2.3 years) and healthy control group (n=40, 52.5% girls, median age: 13.2±2.2 years) were comparable in terms of gender, age and puberty stage. Mean carotid intima-media thickness was higher in obese children than the healthy control group (p=0.002). There was no difference between the two groups in terms of fibrin monomers and D-dimer levels. In obese children, there was a weak negative correlation between mean carotid intima-media thickness and fibrin monomers (p=0.030, r=-0.233). Conclusion: In obese children, mean carotid intima-media thickness was determined higher, as an early indicator of atherosclerosis. We want to emphasize that obese children are at risk for cardiovascular disease and should be evaluated in terms of atherosclerosis. This study investigates the relation between increased carotid intima-media thickness and fibrin monomers, in children, the first time in Literature. What’s already known about this topic? It is possible to reveal the early period of the atherosclerosis process by showing carotid intima medial thickness. Fibrin is a major component of many atherosclerotic plaques. What does this article add? Our study investigated the relationship between mean carotid intima-media thickness in childhood obesity and fibrin monomers. But no positive correlation was found between fibrin monomers and the carotid intima-media thickness.

Failure in the prevention of cross-transmission from contaminated gloves has been recognized as an important factor that contributes to the spread of several healthcare-associated infections. Ex situ coating process with silver nanoparticles (AgNPs) using Eucalyptus citriodora ethanolic leaf extract as reducing and capping agents to coat glove surfaces has been developed to prevent this mode of transmission. Elemental analysis of coated gloves showed 24.8 Wt% silver densely adhere on the glove surface. The coated gloves fully eradicated important hospital-acquired pathogens including Gram-positive bacteria, Gram-negative bacteria, and yeasts within 1 h. The coated gloves showed significant reduction, an average of 5 logs when tested against all standard strains and most clinical isolates (p < 0.01). Following prolonged exposure, the coating significantly reduced the numbers of most adhered pathogenic species, compared with uncoated gloves (p < 0.0001), which was observed by fluorescence microscopy. Scanning electron microscopy further confirmed that AgNPs coated-gloves reduced microbial adhesion of mixed-species biofilms, compared with uncoated gloves. A series of contamination and transmission assays demonstrated no transmission of viable organisms. Biocompatibility analysis confirmed high cell viability of HaCaT and L929 cells at all concentrations of AgNPs tested. The coated gloves were non-toxic with direct contact with L929 cells.

The Sabatier process is promising for carbon dioxide utilization and energy storage. However, the serious problem that limits more comprehensive industrial applications is catalyst deactivation due to the temperature runaway phenomenon. The inert particle dilution approach, including the mixing dilution method and layered dilution method is applied to solve this problem. Based on the lattice kinetic scheme-lattice Boltzmann method (LKS-LBM), the effects of three parameters in bed dilution structure reconstructed by the discrete element method (DEM) on temperature distribution and carbon conversion rate were discussed, so as to investigate the relationship between packing structure and temperature distribution. Furthermore, numerical results indicated that an optimal bed dilution structure, which not only can control the peak temperature below the critical temperature to avoid coking and sintering of catalyst, but also can improve the carbon conversion rate by almost 18% compared with the structure without dilution under the same circumstance.

One Electrogram-Tracing Tells All: what is the mechanism of this supraventricular tachycardia?Moyuru Hirata, MD*, Yuji Wakamatsu, MD*, Koichi Nagashima, MD, PhD*, Sayaka Kurokawa, MD, PhD*, Naoto Otsuka, MD*, Seina Yagyu, MD*, Shu Hirata, MD*, Toshiko Nakai, MD, PhD*, Yasuo Okumura, MD, PhD*.*Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanCorrespondenceKoichi Nagashima, MD, PhD; Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, JapanTel: +81-3-3972-8111Fax: +81-3-3972-1098E-mail: [email protected] word count: 1036 words, 2 FiguresFunding: (None)Disclosures: (None)The work described was supported by departmental resources only.Keywords: narrow QRS tachycardia, atrioventricular nodal reentrant tachycardia, accessary pathway.

The diagnosis of acute myocarditis (AM) remains challenging because of its diverse clinical manifestations. Thus, a wide range of diagnostic tests may be warranted. Although cardiac magnetic resonance (CMR) is the preferred imaging technique, it may not be applicable in the acute AM phase. Our case report highlights the usefulness and diagnostic accuracy of echocardiographic examination. In the first 2-dimensional echocardiography, the focal echobright was presented. A reduced value of global longitudinal strain, and regional disturbances of segmental myocardial strain, both longitudinal and circumferential, in the epicardial layer, were detected with a good correlation with CMR results.

Managing endangered species in fragmented landscapes requires estimating dispersal rates between populations over contemporary timescales. Here we develop a new method for quantifying recent dispersal using genetic pedigree data for close and distant kin. Specifically, we describe an approach that infers missing shared ancestors between pairs of kin in habitat patches across a fragmented landscape. We then apply a stepping-stone model to assign unsampled individuals in the pedigree to probable locations based on minimizing the number of movements required to produce the observed locations in sampled kin pairs. Finally, we use all pairs of reconstructed parent-offspring sets to estimate dispersal rates between habitat patches under a Bayesian model. Our approach measures connectivity over the timescale represented by the small number of generations contained within the pedigree and so is appropriate for estimating the impacts of recent habitat changes due to human activity. We used our method to estimate recent movement between newly discovered populations of threatened Eastern Massasauga Rattlesnakes (Sistrurus catenatus) using data from 2996 RAD-based genetic loci. Our pedigree analyses found no evidence for contemporary connectivity between five genetic groups, but, as validation of our approach, showed high dispersal rates between sample sites within a single genetic cluster. We conclude that these five genetic clusters of Eastern Massasauga Rattlesnakes have small numbers of resident snakes and are demographically isolated conservation units. More broadly, our methodology can be widely applied to determine contemporary connectivity rates, independent of bias from shared genetic similarity due to ancestry that impacts other approaches.