Aim: To summarise the effectiveness of organisational interventions on appropriate opioid use for non-cancer pain upon hospital discharge. Methods: A systematic search was conducted on six electronic databases by two independent reviewers. We included original research articles reporting on quantitative outcomes of organisational interventions targeting appropriate opioid use on hospital discharge. Quality assessment was performed by two independent reviewers. The protocol for this review was prospectively registered on PROSPERO (ID: CRD42020156104). Results: Out of 173 full texts assessed for eligibility, 43 were included in this review. The majority of studies had a moderate to serious risk of bias (33 out of 43). Most of the studies implemented a multifaceted organisational intervention (16 studies). Other interventions included guideline implementation, prescriber education and default opioid prescribing quantity changes in electronic medical records. Multiple studies found that the dissemination of patient-specific and procedure-specific guidelines reduced the quantity of opioids prescribed by 44-57%. Prescriber education provided with feedback was implemented in four studies and resulted in a 33-44% decrease in prescribing rates. Lowering the default quantities in the electronic medical records produced a 40% decrease in opioids prescribed in one study. Conclusion: Guideline implementation, prescriber education and default opioid prescribing quantity changes all appear effective in improving the appropriate use of opioids on hospital discharge. However, the extent of reduction of opioid prescribing upon hospital discharge after the implementation of multifaceted intervention strategies appears similar to that of simpler interventions which require fewer resources.

Growing body of evidence supporting the use ofBivalirudin as alternative anticoagulation during extracorporeal membrane oxygenation.

The MitraClip technique has been increasingly used for correction of mitral valve regurgitation in patients in whom surgical mitral repair is considered contraindicated or very risky, but off label use occurs often. Failure of the procedure, translated into moderate to severe rates of residual or recurrent mitral regurgitation, is observed in up to one-third of the patients, and surgery has been used to correct it in a number of cases, in what can be called an “operation for the inoperable”. That is precisely the subtitle of a paper published in this issue of the JOCS by Gerfen and colleagues, who analyse their institutional experience with a series of 17 patients. In this Editorial, I comment on this series and the possible reasons for failure of the MitraClip, and on the indications for reintervention and its constraints, which I hope can contribute to the discussion about “further exploration and refinement of patient selection criteria and identify predictors for MitraClip failure”, as the authors suggest.

The dominant method for generating Chinese hamster ovary (CHO) cell lines that produce high titers of biotherapeutic proteins utilizes selectable markers such as dihydrofolate reductase (Dhfr) or glutamine synthetase (Gs), alongside inhibitory compounds like methotrexate (MTX) or methionine sulfoximine (MSX), respectively. Recent work has shown the importance of asparaginase (Aspg) for growth in media lacking glutamine–the selection medium for Gs-based selection systems. We generated a Gs/Aspg double knockout CHO cell line and evaluated its utility as a novel dual selectable system via co-transfection of Gs-Enbrel and Aspg-Enbrel plasmids. Using the same selection conditions as the standard Gs system, the resulting cells from the Gs/Aspg dual selection showed substantially improved specific productivity and titer compared to the standard Gs selection method, however, with reduced growth rate and viability. Following adaptation in selection medium, the cells improved viability and growth while still achieving ~5-fold higher specific productivity and ~3-fold higher titer than Gs selection alone. We anticipate that with further optimization of culture medium and selection conditions this approach would serve as an effective addition to workflows for the industrial production of recombinant biotherapeutics.

Background Data on the postoperative outcomes for patients with infective endocarditis complicated by an aortic root abscess is sparse due to the condition’s low incidence and high mortality rates. This systematic review and meta-analysis aims to evaluate existing data on the impact of aortic root abscesses (ARA) on the postoperative outcomes of surgically managed infective endocarditis (IE) and to inform optimal surgical approach. Methods The online databases MEDLINE, EMBASE and Cochrane library were searched from 1990 to 2022 for studies comparing ARA with NARA (no ARA) in infective endocarditis. Data was extracted by two independent investigators and aggregated in a random-effects model (Review Manager version 5.3). Risk of bias was assessed using an adapted version of the Newcastle-Ottawa scale. Results Six clinical studies were included in the meta-analysis (n = 1982). The ARA group was associated with an increased risk of in-hospital mortality (OR = 1.74 96% CI 1.18-2.56) and late mortality (HR = 1.27 95% CI 1.03-1.58). The reoperation meta-analysis was complicated by high rates of heterogeneity (I 2 = 59%) and found no significant differences in reoperation between group ARA and NARA (no ARA) (HR = 1.48; 95% CI 0.92-2.40). Post-hoc scatter graph showed a strong linear relationship (r=0.998), suggesting hospitals with higher rates of aortic root replacement (ARR) achieve lower rates of reoperation for ARA patients compared with PR. Conclusions The presence of an ARA in aortic valve endocarditis is associated with elevated early and late mortality despite modern standards of care. Additionally, ARR should be considered to have a favourable postoperative profile for use in this context.

Objective: To evaluate the functional capacity, pulmonary function and quality of life of children and adolescents with sickle cell anemia (SCA) and to test the reproducibility of functional capacity tests in this population. Method: Cross-sectional study with  volunteers with SCA genotype Hb-SS (SCAG), aged 6 to 18 years matched in age and  gender to the control group (CG). Spirometry, 5-repetition sit-to-stand test (5STS-test),  modified shuttle walk test (MSWT), and Pediatric Quality of Life Questionnaire (PedsQL) were performed. The reproducibility of 5STS-test and MSWT was evaluated:   Results: 48 volunteers of SCAG and 48 of CG were evaluated. Pulmonary function of SCAG (FVC: 92 ± 15% pred.; FEV 1 /FVC: 84 ± 8% pred.) was worse than the CG (104 ± 15% pred.; FEV 1 /FVC: 90 ± 6% pred.) p < 0.05. SCAG had worse functional capacity registered by distance walked: 576m (515-672m) and 5STS-test: 8 seconds (7.4-8.9seconds) compared to the CG who showed distance walked: 1010m (887- 1219m) and 5STS-test: 7 seconds (7.0-8.1seconds), p < 0.001. SCAG had worse quality compared to CG, p < 0.05. The reproducibility was good of MSWT (ICC 0.99 (0.98-0.99 IC-95%)) and 5STS-test (ICC 0.80 (0.69 – 0.88), p < 0.001 . Conclusion: Children and adolescents with sickle cell anemia showed worse capacity to walk or run, and to perform sit-to-stand test. Additionally, they have poor quality of life when compared with their control peers. The MSWT and 5STS-test showed reproducible to be applied in pediatric individual with SCA.

Remdesivir can precipitate fatal acute necrotizing pancreatitis especially in patients who previously suffer from hypertriglyceridemia.

Rationale: As a result of the SARS-CoV-2 pandemic, all pediatric pulmonary fellowship programs conducted virtual interviews for the first time in the Fall of 2020. This study aimed to understand the accuracy of virtual-interview derived-impressions of fellowship programs, as well as applicant preference for future fellowship interview cycles. Methods: A group of pediatric pulmonary fellows and Program Directors designed a REDCap survey. The survey was distributed to all first-year pediatric pulmonary fellows who participated in the 2020-2021 virtual interview season. Results: 23/52 (44%) of first-year pediatric pulmonary fellows completed the survey. 96% were able to form general impressions about fellowship programs during their virtual interviews. 96% reported that generally their fellowship experience matched their virtual-interview derived-impressions. 17 of 19 factors applicants use to rank programs had no statistically significant change (p > 0.05) in impression from virtual interview to fellowship experience. The two factors with a statistically significant (p < 0.05) change in impression were patient care related – volume of ‘bread and butter’ pediatric pulmonary patients and volume of tertiary care pediatric pulmonary patients. 87% prefer some form of in-person interview option in future application cycles. A tiered interview format in which applicants are first invited to a virtual interview day followed by an optional in-person second look day was the most popular preference for future interview cycles (48%). Conclusions: Virtual interviews may provide accurate representations of pediatric pulmonary fellowship programs and applicants prefer some type of in-person interview option in future application cycles.

The file provides a rare audio-recording of typical sound of infective endocarditis (IE) in an adult with patent ductus arteriosus (PDA). It is important to consider PDA-associated IE if pan-systolic murmur is heard in the 2nd intercostal space along the left sternal border, radiating to the left subclavian region.

Squamous cell carcinoma is one of the most common head and neck types of skin cancer. This main objective of this paper is to present a case of a patient who had a moderately differentiated squamous cell carcinoma of the nose and whose tumor had an aggressive growth.

Genetic variation is described from the perspective of an individual. All the different levels of genetic information and variation are covered, ranging from whether an organism is unmixed or hybrid, has variations in genome, chromosomes and more locally in DNA regions, epigenetic variants or alterations in selfish genetic elements. Genetic constitution and heterogeneity of microbiota are highly relevant for health and wellbeing of an individual. Mutation rates vary widely for variation types e.g. due to sequence context. Genetic information guides numerous aspects in organisms. Types of inheritance, whether Mendelian or non-Mendelian, zygosity, sexual reproduction and sex determination are covered. Functions of DNA and functional effects of variations are introduced, along with mechanism that reduce and modulate functional effects, including TARAR countermeasures and intraindividual genetic conflict. TARAR countermeasures for tolerance, avoidance, repair, attenuation and resistance are essential for life, integrity of genetic information and gene expression. The genetic composition, effects of variations and their expression are considered also in diseases and personalized medicine. The text synthesizes knowledge and insight on individual genetic heterogeneity and organizes and systematizes the central concepts.

In this paper, we obtain the solutions of the difference equation \begin{equation*} x_{n+1}=\frac{x_{n-(9 t+8)}}{1+\prod_{k=0}^{6} x_{n-(t+1) k-t}}, \end{equation*} where the initials are positive real numbers.

This paper investigates stochastic differential equations (SDEs) with locally one-sided Lipschitz coefficients. Apart from the local one-sided Lipschitz condition, a more general condition is introduced to replace the monotone condition. Then, in terms of the Euler’s polygonal line method, the existence and uniqueness of solutions for SDEs is established. In the meanwhile, the $p$th moment boundedness of solutions is also provided.

In this paper, the periodicity of a class of nonautonomous fuzzy neural networks with impulses, reaction-diffusion terms and distributed time delays are investigated. Some new sufficient conditions for the existence of periodic solutions and global exponential stability of the systems are obtained using time delays integral differential inequalities, Poincaré mappings and fixed point theory. The validity and generality of the methods are illustrated by two numerical examples.

The gratings contain transmission gratings and reflective gratings. The textbook-screen in the grating experiments is a planar screen. To study the orientation-dependence of the 2-dimention diffraction patterns of the grating, we proposed the cylindrical screen. Then utilizing the cylindrical screen in both transmission grating experiments and reflective grating experiments. Experiments show the 2-dimention curved, expanded and inclined diffraction patterns. The cylindrical screen visually shows that the diffraction orders of the rotating gratings distribute in two dimensions. The CCD can be placed at the precise locations of each order to collect data. By using the cylindrical screen, two coordinates are needed to describe the curved, expanded and inclined diffraction patterns of the rotating grating. The cylindrical screen may be used to test the theories of the grating rotating around 3 axes.

Researchers have used both soil nematode data and soil multifunctionality data as indicators of soil quality. However, the relationship between soil nematodes and soil multifunctionality is poorly understood. This study explored the relationship between soil nematode properties and soil multifunctionality in different land-use types in a subtropical karst region of Southwest China. We selected the following five typical land-use types that differ in the degree of soil disturbance: cropland (maize-soybean), sugarcane, mulberry, forage grass, and forest. Soil multifunctionality was calculated based on bulk density (BD), soil pH, the ratio of soil organic carbon to total nitrogen (C: N), the contents of soil water (SWC), soil total nitrogen (TN), soil organic carbon content (SOC), calcium (Ca), magnesium (Mg), microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), ammonium nitrogen (AN), and nitrate nitrogen (NN). We found that the abundance, Simpson dominance index, and metabolic footprint of soil nematodes were highest in the forest, followed by sugarcane, cropland (maize-soybean) and forage grass, and mulberry. Soil multifunctionality was significantly higher in the forest than in the other land-use types. Soil multifunctionality was positively correlated with the abundance of total nematodes and all nematode trophic groups except omnivores. A random forest model revealed that the dominant nematode genera (i.e., Coomansus and Acrobeloides) and the rare genera (i.e., Wilsonema and Heterocephalobus) were closely associated with soil multifunctionality. Our results suggest that the soil nematodes (especially keystone genera) may mediate the effects of ecosystem disturbance on soil multifunctionality. These findings increase our understanding of the relationships between soil organisms and soil multifunctionality.

The clinical application evaluation of non-invasive imaging in transcatheter aortic valve implantation has also gradually developed. The advantages of ultrasound are gradually revealed in the evaluation of cardiac function before, during and after surgery, as well as short-term and long-term follow-up. Speckle tracking echocardiography (STE) is a non-invasive and angle-dependent new ultrasound diagnostic technique, which is used to evaluate the multi-angle and multi-directional motion velocity, strain and strain rate of human myocardium. The prognosis, recovery and risk stratification have good predictive evaluation value. With the continuous development of new related technologies and parameters from STE, scholars continue to apply these new technologies and new parameters to the clinical evaluation of transcatheter aortic valve implantation. A review of the clinical application of aortic valve implantation.

Abstract Background: The misattribution of an adverse drug reaction (ADR) as a symptom or illness can lead to the prescribing of additional medication, referred to as a prescribing cascade. The aim of this systematic review is to identify published prescribing cascades in community-dwelling adults. Methods: Systematic review reported in line with the PRISMA guidelines and pre-registered with PROSPERO. Electronic databases (Medline (Ovid), EMBASE, PsycINFO, CINAHL, Cochrane Library) and grey literature sources were searched. Inclusion criteria: Community-dwelling adults; Risk-prescription medication; Outcomes-initiation of new medicine to ‘treat’ or reduce ADR risk; Study type-cohort, cross-sectional, case-control and case-series studies. Title/abstract screening, full-text screening, data extraction and methodological quality assessment was conducted independently in duplicate. A narrative synthesis was conducted. Results: A total of 101 studies (reported in 103 publications) were included. Study sample sizes ranged from 126 to 11,593,989 participants and 15 studies examined older adults specifically (≥60 years). Seventy-eight of 101 studies reported a potential prescribing cascade including calcium channel blockers to loop diuretic (n=5), amiodarone to levothyroxine (n=5), inhaled corticosteroid to topical antifungal (n=4), antipsychotic to anti-Parkinson drug (n=4), and acetylcholinesterase inhibitor to urinary incontinence drugs (n=4). Identified prescribing cascades occurred within three months to one year following initial medication. Methodological quality varied across included studies. Conclusion and implications: Prescribing cascades occur for a broad range of medications. ADRs should be included in the differential diagnosis for patients presenting with new symptoms, particularly older adults and those who started a new medication in the preceding 12 months. Word count: 245

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) and anti-threonyl-tRNA synthetase (anti-PL-7) are myositis-specific autoantibodies, associated with rapidly progressive interstitial lung disease (RP-ILD). A 41-year-old woman presented productive cough, dyspnea, and muscle pain. Anti-MDA5 and anti-PL-7 were double-positive. The patient was diagnosed with dermatomyositis-associated ILD, and responded successfully to glucocorticoids and immunosuppressants.

Dexamethasone can reduce post-operative pain and swelling. An appropriate administration of dexamethasone for dental surgical procedures may be local submucosal infiltration. Local delivery may produce a faster onset with more drug at the desired site of action. A single submucosal dose will unlikely produce side effects.

The objective of this study was to investigate diversity, relative abundance, and distribution of medium and large mammals in Mago National Park (MNP), Southern Ethiopia. Data collection was conducted during dry and wet seasons. A systematic sampling design was used to establish line transects along the three main habitat types, namely: Woodland, Acacia savanna, and Riverine forest. A total of 45 line transects were established through the habitats, varing in length from 1.5 to 5 km, depending on the size of the habitat. Twenty-eight medium and large mammals species were recorded in the area belonging to 8 families and 5 orders. Order Artiodactyla had the highest number of species (14 species), followed by Carnivora (8 species), whereas Perissodactyla and Proboscidea were represented by one species each. During both seasons, the highest species diversity (H’ = 2.81, and H’=2.96) was recorded in woodland habitat, but the lowest ( H’ =2.5 and H’= 2.67) in riverine forest. In terms of abundance, Tragelaphus imberbis 1773±86 (12%) was the most abundant species, while Vulpes chama was the least abundant species 104 ±13 that contributed less than 1% of the total. Most of the mammals species occurred in woodland habitat as compared to the other habitat types. Seasonal variation in abundance (number) of individuals of medium and large mammals was significantly different (X2 = 91.651, df =1, p<0.05). However, variation in species composition was not significant (X2 = 0.018, df = 1, P<0.05). It can be concluded that, Mago National Park harbour high species diversity of medium and large mammals. Conservation efoforts that could suatain the high diversity pf the species in the area in needed to main the diversity.

Catheter ablation for tachyarrhythmia via superior approach has been used in patients without possible inferior vena cava access such as in cases of venous occlusion or complex anomaly. Difficulty in catheter manipulation, instability, number of required vascular access, and radiation exposure of operator had been described in the procedure. Application of three-dimensional (3-D) mapping system in catheter ablation via superior approach could navigate the guiding catheter and provide more precise ablation. We reported four cases receiving catheter ablation due to atrioventricular nodal reentry tachycardia, atrial fibrillation and right ventricular arrhythmia via superior approach facilitated by 3-D mapping system with fewer vascular access and catheters.

Though rare, atrio-esophageal fistula is the second most common complication of cardiac catheter ablation for atrial fibrillation; acute cardiac tamponade being the leading cause [1]. We report a case of a 64-year-old male with AEF after a catheter ablation procedure for AF, that proved to be fatal.

Excess biuret, a common impurity in urea fertilizers, is toxic to plants. Little is known about the mechanisms of biuret toxicity in plants. A previous study had shown that transgenic rice ( Oryza sativa) plants overexpressing bacterial biuret hydrolase improved biuret tolerance. Additionally, the biuret hydrolase-overexpressing plants showed a higher 15N ratio than wild-type plants when the roots were fed 15N-labeled biuret. Here, we determined biuret accumulation in rice seedlings by directly measuring the biuret. We found that the biuret hydrolase-overexpressing plants did not contain biuret, whereas wild-type plants accumulated biuret in shoots in the order of mmol L -1 tissue water. We also found that the concentration of allantoin, a nitrogen-rich intermediate compound in the purine degradation pathway, in rice shoots under biuret toxicity was higher than those in control conditions. Inhibition of allantoinase activity by biuret was not detected, and allantoin accumulation appeared to be associated with changes in the expression of putative allantoin transporter genes. Furthermore, another nitrogenous compound citrulline, which is a nonprotein amino acid, accumulated in rice suspension cells under biuret toxicity. The accumulation of these two nitrogen-rich compounds suggests that rice plants subjected to biuret toxicity may need to reduce the generation of surplus ammonium ions.