Objective To identify modifiable and non-modifiable risk factors for severe obstetric anal sphincter injury (OASI) following vaginal delivery. Design Retrospective case-control study. Setting Single center maternity clinic in South-Eastern Norway Population Women diagnosed with OASI following singleton vaginal birth after 30 weeks’ gestation (n = 421) and matched controls (n = 421) during 1990-2002. Methods Data were extracted retrospectively from an institutional birth registry. For each woman with OASI the first subsequent vaginal singleton delivery matched for parity was elected as control. Potential determinants for OASI were assessed by conditional logistic regression analyses. Main outcome measure OASI, defined as 3rd or 4th degree obstetric anal sphincter lesions. Results Among modifiable factors amniotomy was the strongest independent determinant for OASI in both primi- (adjusted odds ratio [aOR] 4.84; 95% CI 2.60–9.02) and multiparous (aOR 3.76; 95% CI 1.45–9.76) women, followed by augmentation with oxytocin (primiparous: aOR 1.63; 95% CI 1.08–2.46, multiparous: aOR 3.70; 95% CI 1.79–7.67). Vacuum extraction and forceps delivery were independently associated with OASI in primiparous women (vacuum: aOR 1.91; 95% CI 1.03–3.57, forceps: aOR 2.37; 95% CI 1.14–4.92), and episiotomy for OASI in multiparous women (aOR 2.64; 95% CI 1.36–5.14). Conclusions Amniotomy may be a hitherto unrecognized independent modifiable risk factor for OASI and should be further investigated for its potential role in preventive strategies for OASI. Funding Innlandet Hospital Trust research fund, grant number 150434. Keywords Obstetric anal sphincter injury; OASI; Birth; Birth injury; Modifiable risk factor; Amniotomy.

Metabarcoding provides a powerful tool for investigating biodiversity and trophic interactions, but the high sensitivity of this methodology makes it vulnerable to errors, resulting in artefacts in the final data. Metabarcoding studies thus often utilise minimum sequence copy thresholds (MSCTs) to remove artefacts that remain in datasets; however, there is no consensus on best practice for the use of MSCTs. To mitigate erroneous reporting of results and inconsistencies, this study discusses and provides guidance for best-practice filtering of metabarcoding data for the ascertainment of conservative and accurate data. The most common MSCTs identified in the literature were applied to example datasets of Eurasian otter (Lutra lutra) and cereal crop spider (Araneae: Linyphiidae and Lycosidae) diets. Changes in both the method and threshold value considerably affected the resultant data. Of the MSCTs tested, it was concluded that the optimal method for the examples given combined a sample-based threshold with removal of maximum taxon contamination, providing stringent filtering of artefacts whilst retaining target data. Choice of threshold value differed between datasets due to variation in artefact abundance and sequencing depth, thus studies should employ controls (mock communities, negative controls with no DNA and unused MID-tag combinations) to select threshold values appropriate for each individual study.

Potential cancer risk with omalizumab: a disproportionality analysis

Background and aims: Activation wavefront is rapid and uniform in normal myocardium. Fibrosis is associated with deceleration zones (DZ) and late activated zones. Our aim was to study the right ventricular outflow tract (RVOT) endocardial activation duration (EAD) in sinus rhythm, and assess the presence of DZs, in patients with PVCs and controls. Methods: We studied 29 patients with idiopathic PVCs from the outflow tract, subjected to catheter ablation and an activation and voltage map of the RVOT in sinus rhythm. A control group of 15 patients without PVCs that underwent ablation of supraventricular arrhythmias was also studied. The RVOT EAD and number of 10 ms isochrones were assessed. DZ were defined as a zone with>3 isochrones within 1 cm radius. Low voltage areas (LVA) defined as areas with local electrogram amplitude <1.5mV. Results: The two groups did not differ in relation to age, gender or number of points in the map. EAD and number of 10 ms isochrones were higher in the PVC group; 56 (41-66) ms vs 39 (35-41) ms, p=0.001 and 5 (4-8) vs 4 (4-5), p=0.001. Presence of DZs and LVAs were more frequent in the PVC group; 20 (69%) vs 0 (0%), p<0.0001 and 21 (72%) vs 0 (0%), p<0.0001. Patients with LVAs had longer EAD 60 (52-67) vs 36 (32-40) ms, p<0.0001. Conclusions: EAD was longer and DZs were more frequent in patients with PVCs and were associated with presence of LVAs.

Introduction: There are a lack of potentially inappropriate medications (PIMs) predictors among the geriatric population with cardiovascular disease (CVD). Objective: This study was focussed on finding out the predictors and prevalence of PIMs use in the older adult patients hospitalized with cardiovascular disease. Methods: This prospective cross-sectional study included 250 older adult patients (mean age 69.03± 5.76 years) with the CVD having age 65 years or more, admitted in the cardiology/medicine department of a tertiary care hospital. PIMs were identified as per Beers criteria 2019. Binary Logistic regression analysis was used to determine the predictors of PIMs use in older adult patients. Results: Results indicate a very high PIM prescription rate of more than 62.4% (n= 156) with Proton pump inhibitor, short acting insulin according to sliding scale, Enoxaparin <30ml/min as the most commonly prescribed PIMs. On Binary logistic regression, important predictors for PIMs use were found to be females (odds ratio [OR] 2.36, 95% confidence interval (CI) 1.36- 4.09, P= 0.002), three diagnosis (OR 4.29, 95% CI 1.31- 14.0, P= 0.016), ≥4 diagnosis (OR 4.8, 95% CI 1.49- 15.44, P= 0.009), 7-9 days of hospital stay (OR 4.74, 95% CI 1.07- 20.96, P= 0.04), ≥ 9 medications per day (OR 0.09, 95% CI 0.01- 0.50, P= 0.006). Conclusion: The prevalence of PIMs in older adults with cardiovascular disease is very high, and females with CVD have emerged as a potential PIM indicator. The study also indicates a lack of awareness towards Beer criteria in health care workers (physicians/pharmacists/nursing staff) leading to PIM.

Objective: In this study, we aim to evaluate the content and quality of the most relevant YouTube videos related to Holmium laser enucleation of the prostate (HoLEP) surgery. Materials and Methods: The keywords ‘HOLEP’, ‘laser enucleation’ and ‘prostate enucleation’ were used to perform a search on YouTube. Non-English language videos, videos with less than 4-minute duration, and repetitive videos were excluded. The reactions of the viewers to the videos were evaluated by recording the ‘total views’, ‘views/month’ and ‘likes and dislikes’ parameters. The data were divided into two groups based on the source of upload: Group 1 consisted of healthcare providers and Groups 2 comprised commercial companies and for-profit organizations. Results: A total of 117 videos were included in the study. A significant portion of the videos (77.7%) had been uploaded by healthcare providers. There was no statistically significant difference between the uploading groups in terms of the DISCERN and GQS scores (p=0.484 and p=0.108, respectively). However, the PEMAT understandability and actionability scores were statistically significantly higher in Group 2 (p=0.004 and p=0.022, respectively). In addition, when the misinformation scale was evaluated, there were significantly more videos with high-degree misinformation in Group 2 (5.5% vs 33.3, p=0.001). Conclusion: On video sharing platforms, such as YouTube, the number of reliable videos with accurate and appropriate guidance about diseases and treatments should be increased, and these videos should be allowed to be posted after they have been approved by relevant institutions, including healthcare associations and universities.

Chronic rhinosinusitis (CRS) is a common clinical syndrome that produces significant morbidity and costs to our health system. The study of CRS has progressed from an era focused on phenotype to include endotype based information. Phenotypic classification has identified clinical heterogeneity in CRS based on endoscopically observed features such as presence of nasal polyps, presence of comorbid or systemic diseases and timing of disease onset. More recently, laboratory-based findings have established CRS endotype based upon specific mechanisms or molecular biomarkers. Understanding the basis of widespread heterogeneity in the manifestations of CRS is advanced by findings that the three main endotypes, Type 1, 2 and 3, orchestrate the expression of three distinct large sets of genes. The development and use of improved methods of endotyping disease in the clinic is ushering in an expansion of the use of biological therapies targeting Type 2 inflammation now and perhaps other inflammatory endotypes in the near future. The purpose of this review is to discuss the phenotypic and endotypic heterogeneity of CRS from the perspective of advancing the understanding of the pathogenesis and improvement of treatment approaches and outcomes.

The utilization and popularization of biodiesel are always limited by its poor cold flow properties. Both bio-based alcohol and diesel from direct coal liquefaction (DDCL) has potential to enhance the cold flow properties of biodiesel. Ternary blends of waste cooking oil biodiesel (BWCO) with DDCL and bio-based ethanol (ET) or 1-butanol (BT) for improving the cold flow properties of biodiesel. The pour point (PP), cold filter plugging point (CFPP), and cloud point (CP) of BWCO-ET, BWCO-BT, and BWCO-DDCL binary blends, and BWCO-ET-DDCL and BWCO-BT-DDCL ternary blends were comparatively assessed. Ternary phase diagrams were also applied into analyze the blending effect of the three components on the cold flow properties of biodiesel. Results showed that both DDCL, ET and BT can remarkably enhance the cold flow properties of BWCO. BT and DDCL presented a better synergistic depression effect. For ternary blends in 20:10:70 blending ratio, BWCO-BT-DDCL exhibited the lowest PP, CFPP, and CP of −23 °C, −19 °C, and −17 °C, respectively. The crystallization behavior and crystal morphology of blended fuels are also observed via a polarizing optical microscope, and find that DDCL together with BT in biodiesel can effectively retard the aggregation of large crystals and inhibit crystals growth.

One of the hallmarks of COVID-19 is the cytokine storm that provokes primarily pneumonia followed by systemic inflammation. Emerging evidence has identified a potential link between elevated levels of interleukin-17A (IL-17A) and disease severity and progression. Considering that per se IL-17A can activate several inflammatory pathways, it is plausible to hypothesize an involvement of this cytokine in COVID-19 clinical outcomes. Thus, this cytokine can represent a marker of disease progression and/or a target to develop therapeutic strategies. This hypothesis paper aims to propose this “unique” cytokine as a silent amplifier of the COVID-19 immune response and (potentially) related therapy.

A case series of 22 patients with confirmed SARS-CoV-2 infection and Corona Virus Disease 2019 (COVID-19) symptoms was followed in a primary care clinic. We provided quantitative and longitudinal profiling for SARS-CoV-2 IgM and IgG with a point of care device. Half the patients had a history of anosmia or ageusia. IgM and IgG responses were highly heterogeneous quantitatively and temporally. We determined that clinical symptomatology of chemosensory loss correlated with lesser but sustained titers of IgM and IgG whereas normal chemosensation correlated with transiently higher but rapidly declining antibody levels.

Background The delivery of Radiation therapy (RT) needs a level of coordination and planning which can be challenging in resource-limited settings. In this retrospective study we describe the profile of children undergoing radiation and analyze deviation from accepted norms. Procedure Data on all children (< 18 years age) with cancer who completed RT from Jan 2009 to Dec 2019 were retrieved. Diagnostic groups with more than 5 patients, were included in the analysis for deviations in RT (Time to start (TTS); total dose delivered (TDD) in Grays; and time to complete (TTC)). We investigated reasons for deviation. Results 207 received RT as front-line treatment (68% Indian, 59% male and 32% received treatment preceding RT outside). Most common diagnosis were brain tumors (44%), lymphoma (13%). leukemia and soft tissue sarcoma (10% each). 23.6% had deviation in TTS, 6.0% in TDD and 24.7% in TTC while 43.4% had at least one deviation in any of these three parameters. Deviation in TTS varied significantly by location of preceding treatment and by cancer (greatest deviation in sarcomas) with issues around access to healthcare the most common reason. Deviation in TTC varied significantly by cancer (greatest deviation in sarcomas and medulloblastoma) with myelotoxicity the most common reason. Conclusions Our study adds to the limited literature on RT quality for children with cancer in LMIC. Certain cancers (sarcomas and medulloblastoma) and patient groups (preceding treatment outside our institute) had the maximum deviation. Barriers to accessing care and myelotoxicity were the two main reasons for this deviation.

Legends of Allergy/Immunology: Robert P. Schleimer

Plant phenology is manifested in the seasonal timing of flowering and vegetative processes, but also has ontogenetic aspects. The adaptive basis of seasonal phenology has been considered mainly in terms of climatic drivers. However, some biotic factors as likely evolutionary influences on plants’ phenology appear to have been under-researched. Several specific cases of putative biotic factors driving plant phenology are outlined, involving both herbivores and pathogens. These illustrate the diversity of likely interactions rather than any systematic coverage or review. Emphasis is on woody perennials, in which phenology is often most multi-faceted and complicated by the ontogenetic aspect. The timing and duration of shoot flushing may in at least some cases contribute to defencses against herbivores, largely through brief periods of ‘predator satiation’ when plant tissues have highest food value. However, the complete seasonal leaf fall that characterizes deciduous plants may be a very important defencse against some pathogens. Whether biotic influences drive acquisition or ‘biotic lock-in’ of deciduousness is considered. In one case; of leaf rusts in poplars, countervailing influences of the rusts and climate suggest lock-in. Often, however, biotic and environmental influences likely reinforce each other. Wide re-examination of plant phenology, accommodating the roles of biotic factors and their interplays with environments as additional adaptive drivers, is advocated, towards developing and applying hypotheses that are observationally or experimentally testable.

The evolution of floral traits is largely attributed to pollinator-mediated selection; however, the importance of pollinators as selective agents in pollen-limited environments is poorly resolved. In pollen-limited arctic and subarctic regions, selection is expected to either favor floral traits that increase pollinator attraction or promote reproductive assurance through selfing. We quantified phenotypic selection on floral traits in two arctic and two subarctic populations of Parrya nudicaulis. Additionally, we measured selection in plants in both open-pollination and pollen-augmentation treatments to estimate selection imposed by pollinators in one population. Seed production was found to be limited by pollen availability and strong directional selection on flower number was observed. We did not detect consistently greater magnitudes of selection on floral traits in the arctic relative to the subarctic populations. Directional selection for more pigmented flowers in one arctic population was observed however. In some populations, selection on flower color was found to interact with other traits. We did not detect consistently stronger selection gradients across all traits for plants exposed to pollinator selection relative to those in the pollen-augmentation treatment; however directional selection tended to be higher for some floral traits in open-pollinated plants.

Background: Although congenital erythrocytosis (CE), an inherited disorder, impairs pediatric quality of life, physicians often overlook high hemoglobin (Hgb) levels and its symptoms due to lack of knowledge of age-adjusted pediatric Hgb levels and CE’s rarity. Methods: In a retrospective, single-center study, data from hospital records of patients (<18 years) diagnosed with CE were evaluated. Results: Forty patients from 39 families (male: female ratio = 7:1) had been diagnosed with CE in a 20-year period, at a mean age of 15.31 ± 2.49 years (8.34–17.92) and with mean Hgb levels of 17.4 ± 1.34 g/dL (14.63–23.0). No serum erythropoietin levels exceeded the reference levels. Although the most common symptom was headache (80.0%), 40.0% of patients presented with at least one gastrointestinal symptom (e.g., nausea, vomiting, abdominal pain, and rectal bleeding), and 75.0% exhibited plethora. None had leukocytosis, thrombocytosis, abnormal capillary oxygen saturation, JAK2 mutation, and venous blood gas analysis and Hgb electrophoresis revealed no abnormalities. While 43.6% of patients had family histories of CE, 28.2% had 15–48-year-old relatives who had experienced myocardial infarction, stroke, and/or sudden death. Six asymptomatic patients were detected incidentally. When symptoms of hyperviscosity were present, aspirin was prescribed, and phlebotomy performed. No thrombotic episodes occurred as a result. Conclusion: To detect CE, physicians should assess Hgb levels in consideration of normal age-adjusted levels in children. Pediatric patients with CE may also present with gastrointestinal symptoms. Although no thrombotic episode occurred among the patients, their family histories included life-threatening thrombotic episodes, even in adolescents.

A subtle aortic dissection can be challenging to detect despite the availability of multiple diagnostic modalities. Whilst rare, the inability to detect this variant of aortic dissection can lead to a dismal prognosis. We present an extremely rare case of a subtle aortic dissection with supraannular aortic root intimal tear and acute severe aortic regurgitation in a patient with a bicuspid aortic valve. Initial concerns were either aortic dissection or infective endocarditis. Despite advanced multimodality preoperative imaging, diagnosis was made intraoperatively and a Bentall procedure with a mechanical aortic valve was performed. As current data is limited, a literature review concerning subtle aortic dissection is provided.

Hexagonal chains are a special class of catacondensed benzenoid system and phenylene chains are a class of polycyclic aromatic compounds. Recently, A family of Sombor indices was introduced by Gutman in the chemical graph theory. It had been examined that these indices may be successfully applied on modeling thermodynamic properties of compounds. In this paper, we study the expected values of the Sombor indices in random hexagonal chains, phenylene chains, and consider the Sombor indices of some chemical graphs such as graphene, coronoid systems and carbon nanocones.

Abnormal ostial morphology and acute take-off are considered potential mechanisms of flow obstruction in the anomalous coronary artery. We present a proof of concept describing how three-dimensional transoesophageal echocardiography can be used to visualise the coronary ostium and proximal course in patients with anomalous coronary artery.

The outcome of coronary artery bypass surgery depends on complete revascularization. In our paper, we attempt to demonstrate that Off-pump coronary artery bypass (OPCAB) is applicable to coronary heart disease patients with low LVEF. Low LVEF does not affect cardiac revascularization. Low LVEF is an independent risk factor for the outcome of CABG patients, but it does not mean that the OPCAB procedure leads to poor outcomes. In our hospital, we used on-pump CABG or conventional bypass surgery for coronary heart disease patients with low LVEF before 2010.With the accumulation of cases, OPCAB is now used in more than 95% of coronary artery bypass grafts in our center. Our data suggest that OPCAB is safe and reliable for patients with low LVEF.

Theoretical calculations involving singlet molecular oxygen (O2(1g)) are challeng- ing due to their inherent multi-reference character. We have tested the quality of re- stricted and unrestricted DFT geometries obtained for the reaction between singlet oxy- gen and a series of alkenes (propene, 2-methylpropene, trans-butene, 2-methylbutene and 2,3-dimethylbutene) which are able to follow the ene-reaction. The electronic en- ergy of the obtained geometries are rened using 3 dierent methods which account for the multi-reference character of singlet oxygen. The results show that the mechanism for the ene-reaction is qualitatively dierent when either one or two allylic-hydrogen groups are available for the reaction. When one allylic-hydrogen group is available the UDFT calculations predict a stepwise addition forming a biradical intermediate, while, the RDFT calculations predict a concerted reaction where both hydrogen abstrac- tion and oxygen addition occur simultaneously. When two allylic-hydrogen groups are available for the reaction then UDFT and RDFT predict the same reaction mechanism, namely that the reaction occurs as a stepwise addition without a stable intermediate between the two transition states. The calculated rate constants are in reasonable agreement with experimental data, except for trans-butene where the calculated rate constant is three orders of magnitude lower than the experimental one. In conclusion we nd that the simple bypassing scheme tested in this paper is a robust approach for calculations of reaction involving singlet oxygen in the limit that the transition state processes low multi-reference character. 2

We present the derivation of a new response method termed rst order po- larization propagator approximation. The electronic structure is given by a density functional representation. We provide a detailed derivation of the method along with explicit expressions for the relevant integrals and matrix elements.

The rapid global spread of SARS-CoV-2 and the resulting Coronavirus disease (COVID-19) pandemic has led to urgent efforts to contain and mitigate transmission. The use of face masks became a primary measure to limit the spread, which increased the production and consequent waste generation. It is estimated that globally 129 billion single-use face masks are discharged into the environment every month. Besides to add to already great concerns over plastic pollution, contaminated face masks not properly handled also poses a health risk. The health and environmental consequences caused by the inadequate disposal of single-use face masks are treated in this study as an eminent risk to be properly communicated. This study framed the waste generation as a side impact of the COVID-19 pandemic and analysed how the communication has been made regarding the correct disposal of single-use masks, with focus in users of public transport in Stockholm region. National and regional authorities are recognized as the main responsibles for the communication about correct disposal, together with manufacturers and suppliers of single-use face masks. Disclosure and informative material of four government authorities and instruction manuals of eight brands of single-use face masks are analysed according to: i) presence / absence of information (about the disposal); ii) type of communication (visual or written); iii) message transmitted and; ix) availability in other languages. It was found guidance about correct disposal of face mask in two thirds of the existing communication, that is mainly written and with few visual aids. Half of communication is made only in Swedish and with no sufficient focus on the importance of correct disposal neither with reference to trash bins with lid. It suggests that the current communication about how to dispose single-use masks safely may not be enough, which is affecting the perception of risk by the population and worsening the health and environmental consequences caused by the inadequate disposal.

Background: This study investigated the impact of transplanting center donor acceptance patterns on usage of extended-criteria donors (ECDs) and posttransplant outcomes following orthotopic heart transplantation (OHT). Methods: The Scientific Registry of Transplant Recipients was queried to identify heart donor offers and adult, isolated OHT recipients in the United States from 1/1/2013-10/17/2018. Centers were stratified into 3 equal-size terciles based on donor heart acceptance rates (<13.7%, 13.7%-20.2%, >20.2%). Overall survival was compared between recipients of ECDs (≥40 years, left ventricular ejection fraction <60%, distance ≥500 miles, hepatitis B, hepatitis C or human immunodeficiency virus, or ≥50 offers) and recipients of traditional-criteria donors, and among transplanting terciles. Results: A total of 85,505 donor heart offers were made to 133 centers with 15,264 (17.9%) accepted for OHT. High-acceptance programs (>20.2%) more frequently accepted donors with LVEF <60%, HIV, HCV, and/or HBV, ≥50 offers, or distance >500 miles from the transplanting center (each p<0.001). Posttransplant survival was comparable across all three terciles (p=0.11). One- and five-year survival were also similar across terciles when examining recipients of all five ECD factors. Acceptance tier and increasing acceptance rate were not found to have any impact on mortality in multivariable modeling. Of ECD factors, only age ≥40 years was found to have increased hazards for mortality (HR 1.33, 95% CI 1.22-1.46, p<0.001). Conclusions: Of recipients of ECD hearts, outcomes are similar across center-acceptance terciles. Educating less aggressive programs to increase donor acceptance and ECD utilization may yield higher national rates of OHT without major impact on outcomes.

The timing of germination is a key life-history trait in plants, which is strongly affected by the strength of seed dormancy. Continental-wide variation in seed dormancy has been related to differences in climate and the timing of conditions suitable for seedling establishment. However, for predictions of adaptive potential and consequences of climatic change, information is needed regarding the extent to which seed dormancy varies within climatic regions and the factors driving such variation We planted 17 Italian and 28 Fennoscandian populations of Arabidopsis thaliana in the greenhouse and at two field sites in Italy and Sweden. To identify possible drivers of among-population variation in seed dormancy, we examined the relationship between seed dormancy and climate at the sites where populations were originally sampled. Seed dormancy was on average stronger in the Italian compared to the Fennoscandian populations, but also varied widely within both regions. Estimates of seed dormancy in the three maternal environments were positively correlated, but seeds had on average stronger dormancy when produced in the greenhouse than at the two field sites. Among Fennoscandian populations, seed dormancy tended to increase with increasing summer temperature and decreasing precipitation at the site of origin. In the smaller sample of Italian populations, no significant association was detected between mean seed dormancy and climate at the site of origin. The correlation between seed dormancy and climatic factors in Fennoscandia suggests that at least some of the among-population variation is adaptive and that climate change will affect selection on this trait.