Influenza A virus (IAV) outbreaks constitute a constant threat to public health and pose a remarkable impact on socio-economic systems worldwide. Interactions between wild and domestic birds, humans, and swine can lead to spillover events. Backyard livestock systems in proximity to wetlands represent a high-risk area for viral spread. However, some gaps remain in our knowledge of IAV transmission at the wildlife – livestock interface in Mexico. Hence, the study aimed at molecular identification and phylogenetic characterization of IAV in the wild duck – backyard livestock interface at a wetland of Mexico. A total of 875 animals were tested by real-time RT-PCR (qRT-PCR). We detected IAV in 3.68% of the wild ducks sampled during the winter season 2016 – 2017. Nonetheless, the samples obtained from backyard poultry and swine tested negative. The highest IAV frequency (11.10%) was found in the Mexican duck (Anas diazi). Subtypes H1N1, H3N2, and H5N2 were detected. Phylogenetic analysis of influenza viruses isolated from wild ducks of the Lerma marshes revealed that hemagglutinin (HA) gene sequences were related to waterfowl, swine, and poultry IAV strains previously isolated in the United States and Mexico. In conclusion, the co-circulation of three IAV subtypes in wild ducks close to backyard farms in Mexico, as well as, the local identification of HA gene sequences genetically related to Mexican livestock IAV strains and also to North American waterfowl IAV strains, highlight the importance of the Lerma marshes for influenza surveillance given the close interaction among wild birds, poultry, pigs, and humans.

Baricitinib is a promising drug in COVID-19 pneumonia. The aim of this study is to compare the clinical outcome of moderate-to-severe COVID-19 pneumonia treated with baricitinib with or without a loading dose. This prospective case-control study enrolled 37 adult patients where 17 patients (control) received baricitinib at 4 mg oral daily dose and 20 patients (case) received an additional single 8 mg oral loading dose. The median day to gain blood oxygen saturation level ≥ 95% (in room air) and return in normal breathing function were lower in case group than the control group [29.4% (n = 17)/10% (n = 20), P < 0.05; 11.8% (n = 17)/5% (n = 20), P > 0.05), respectively]. The requirement of intensive care unit and mechanical ventilation support were higher in control group than the case group. Thus, an additional loading dose of baricitinib revealed better clinical outcome in COVID-19 pneumonia.

Background: Computed tomography (CT) is a useful tool for the identification of calcified lesions in the aorta. However, no quantitative evaluation has been established to assess the applicability of simple anastomosis preoperatively. We conducted this retrospective study to establish a reference range of the maximal CT value for application of simple anastomosis. Methods: 122 consecutive patients underwent replacement of the thoracic aorta between 2007-2011, excluding those with acute aortic dissection. The patients were divided into two groups: those who could undergo simple anastomosis (Simple group:n=105), and those who required endarterectomy prior to anastomosis (Manipulation group:n=17). The maximal CT value at the anastomosis site was calculated by an imaging software. Results: The mean maximal CT value (Hounsfield unit: HU) was significantly higher in the Manipulation group (638.1 ± 269.5 [166-1304]) than in the Simple group (94.7 ± 171.5 [0-790]) (p<0.0001). The maximal CT value enabled us to predict the simple anastomosis with the area under the receiver operating characteristic curve of 0.96 (p<0.0001). The cut-off value was 325 HU (sensitivity 94.1%, specificity 81.7%). The 10-year survival rate was significant lower in the Manupilation group (11.8%) than in the Simple group (43.2%). In the multivariate analysis, age (Hazard Ratio [HR]:1.073), Hypertension (HR:2.382) and maximal CT value (HR:1.001) were independently associated with long-term mortality. Conclusions: Preoperative evaluation of the maximal CT value is a useful tool in predicting whether simple anastomosis is applicable or not, in the thoracic aortic surgery. Maximal CT value is a risk factor for long-term mortality.

As an important soil carbon pool in Qinghai-Tibet Plateau (QTP), alpine peatland are extremely sensitive to global change. Duration of drainage and water table drawdown accelerate peatland degradation as the soils are no longer protected by anaerobic condition, which may worsen under climate warming. Hence, the purpose of our study was to evaluate the effect of drainage on microbial characteristics, greenhouse gas (GHG) emissions and their influencing factors, and further analyze whether the the variability of GHG emissions increases with warming. The results showed that the influence of water table drawdown on microbial communities were greater than that of duration of drainage. Both the fungal and prokaryotic community compositions varied with water table gradient, and soil microbiota may served as a biomarker to analyze the differences in GHG emissions among three different water table treatments. Intriguingly, the GHG emission decreased with the increase of drainage age, while water table drawdown reduced the CO2 and CH4 emission rates, and increased N2O emission rates. In addition, high temperature increased CO2 by 75% and N2O by 42%, but not significantly decreased the CH4 emission rates. Structural equation modeling showed that microbe was the primary factor affecting GHG emissions from drained peatlands, especially prokaryotes. Overall, our results indicate that water table has a greater impact on GHG emissions than duration of drainage, and the variability of GHG emissions increases with warming.

Background and Purpose: Obesity and Type 2 Diabetes are major causes of morbidity-mortality characterized by mitochondrial dysfunction and oxidative-nitrosative stress. Despite intensive research, the events that cause the onset and progression of these diseases are not completely understood. Herein, we investigated if dysregulation of mitochondrial dynamics and biogenesis is involved in an animal model of obesity and diabetes. Experimental Approach: Mitochondrial dynamics and biogenesis were evaluated in epididymal white adipose tissue and adipocytes from ob/ob mice, an animal model of obesity and diabetes, pharmacological treatment with mdvi-1, a selective inhibitor of Drp1 and leptin. Key Results: A decrease of Mfn2 and OPA-1 protein expression and an increase in Drp1- protein levels were observed with enhanced and sustained mitochondrial fragmentation in ob/ob mice compared to wt C57BL/6 animals. The content of mitochondrial DNA and mRNA expression of PGC-1α, both parameters of mitochondrial biogenesis, were reduced in ob/ob mice. The treatment with leptin or mdvi-1 (Drp1 inhibitor) significantly increased abnormal biogenesis, improved fusion-to-fission balance and attenuated mitochondrial dysfunction, and adipogenesis, thus inducing white-to-beige adipocyte transdifferentiation. Measurements of glucose and lipid oxidation in adipocytes revealed that both leptin and mdvi-1 increase substrates oxidation while in vivo determination of blood glucose showed decreased blood glucose concentration by 50 % in ob/ob mice, almost to the wt level. Conclusion and Implications: In light of these results, pharmacological targeting of Drp1 may be a potential novel therapeutic tool for obesity and diabetes.

Environmental DNA (eDNA) has increasingly been used in the surveillance of imperiled aquatic species. Despite recent efforts in drawing genetic material from the environment, there are still pitfalls surrounding this field. We created a novel protocol which implements loop-mediated isothermal amplification (LAMP) to detect target DNA. Our methods are applied here in the surveillance of Etheostoma trisella, the Trispot Darter, a freshwater fish that recently received protection under the U.S. Endangered Species Act. Water samples (n = 256) were collected at sites in Alabama and Georgia to determine whether E. trisella still occupies historic sites and whether it inhabits previously unknown areas. We found evidence of E. trisella presence in 69 water samples while 187 were negative. Our LAMP protocol is capable of amplifying low quantities of DNA in the water, and is a robust technique for freshwater species surveillance. Verification of positive results from eDNA experiments is essential to confirm reaction reliability. Application of methods such as ours are necessary for recognizing species under threat that require conservation.

Dear Editor, We really appreciate MN van Ijsselmuiden et al. for their efforts in conducting the first ever multicentre randomized controlled trial to compare laparoscopic sacrohysteropexy (LSH) versus sacrospinous hysteropexy (SSHP) .1 It has raised my queries and questions regarding the methodology and results of this trial. I would like to know the reasons to include the patients with history of previous pelvic floor or prolapse surgery in the exclusion criteria. If those above patients were randomly allocated into two surgical group equally, would it have impacts over the study result or design? Moreover, we are really interested and keen to know how to perform the anterior colporrhaphy and posterior colporrhaphy though laparoscopic method as mentioned in the article.There are more patients presented with anterior vaginal wall prolapse: POP-Q stage- Aa or Ba > 0 (LSH group:81%; SSHP group:72.6%) when compared to apical prolapse (LSH group:46.6%; SSHP:45.6%) in Table 1. It seems that the majority of study population had combined anterior and apical compartment prolapse but not with solely apical prolapse. Furthermore, Table 2 showed that overall anterior compartment failure rates are 50.9% and 56.9% in LSH group and SSHP group respectively in 1-year follow-up interval. The failure rate is extraordinarily high compared with previous study.2 Hysteropexy surgeries are useful to treat patients with sorely apical prolapse but not with patients with combine anterior and apical compartment prolapse with prominent cystocele. In controversy, a large majority were satisfied with the one year surgical results and would recommend the surgery to someone else (LSH: 87.7%; SSHP: 89.7%) even though there was a high recurrence rate of anterior wall prolapse in one year follow-up.In the statistical analysis section, there were significantly more additional anterior vaginal wall repairs in the SSHP group compared to LSH group (SSHP: n = 61, 98.4%; LSH: n = 55, 85.9%, P = 0.010). I would like to know how this small number difference (61-55=6) in these two groups can cause significant difference in P value and how to calculate this P value. This trial assumes a failure rate of 3% based on outcomes of SSHP in a previous prospective study. However, the data population is relatively small while the non-inferiority margin was set at 10%.The primary outcome is defined as a composite outcome of surgical failure of the apical compartment at 12 months’ follow-up, defined as recurrence of uterine prolapse (POP-Q ≥ stage 2). Surgical success was defined as no prolapse beyond the hymen. According to POP-Q stage system, POP-Q stage 2 is defined as most distal prolapse is between 1 cm above and 1 cm beyond hymen.3 The most prominent prolapse which descends beyond hymen would be also considered as stage 2 prolapse. It elicits clinical controversy and conflicts in the definition between surgical failure and success. We hope that this letter will deliver the message that precise preoperative patient selection and study design are crucial as they may have critical impacts over clinical outcomes and treatment success.Min-syuan Huang,2, 3 Zi-Xi Loo,1Kun- Ling Lin,1, 2 Cheng-Yu Long1, 21. Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan2. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan3. Department of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan

Dear editor/Sir,We thank Song et al. for their insightful comments (1) on our article (2) and commend them for their study about human papillomavirus (HPV)-genotyping on self-samples and their analysis on different triage strategies for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) (3). They report that cytology on physician-sampled material has a sensitivity of 74.8% for detecting CIN2+, while HPV-genotyping for 16/18 has a sensitivity of 52.6% for detecting CIN2+. This means that HPV-genotyping in their hands, is still inferior to cytology testing and cannot fully replace this triage strategy. However, adding HPV-genotyping to cytology testing could increase the sensitivity, as has been described by others as well. While our study shows that reflex cytology on self-samples cannot replace triage with regular cytology for HPV-positive women, because of the low sensitivity of 29.4% for detecting CIN2+, it is valuable as an additional method for triage (2). With a positive predictive value (PPV) of 68.1% for detecting CIN2+ it is effective to refer HPV-positive women with abnormal cytology on self-sampling directly for colposcopic evaluation without the requirement of an extra visit to the general practitioner. A PPV of 21.2% for HPV-genotyping for 16/18 on self-samples for detecting CIN2+ is not enough to refer these women directly for colposcopy. We agree that cost-effectiveness is important. It is not sure if 15% of direct referral will completely cover the costs for 85% of double cytology testing. As the collection in PreservCyt (Cytyc Corporation, Boxborough, MA, USA) has already been performed for HPV-testing on the self-samples, extra costs will include the use of ThinPrep slides (Hologic Inc, Marlborough, MA, USA) and cytotechnicians’ time for analysing the slides. On the other hand, there will be a reduction in costs for consulting the general practitioner and for regular cytology testing, including material costs (Cervex brush (Rovers® Medical Devices B.V., Oss, the Netherlands), PreservCyt jar, ThinPrep slide), transportation costs, and cytotechnicians’ time for analysing the slides. However, besides cost-effectiveness, patient comfort is at least as important, as well as reduction in loss-to-follow-up and diagnostic delay, in which the latter also positively influences the costs. It remains a challenge to find a triage method on HPV-positive self-samples which could fully replace regular cytology. Molecular tests, such as methylation markers and microRNA detection, are promising future triage methods (4, 5). They are more objective than cytology testing and highly reproducible, however not ready yet for full implementation in cervical cancer screening. Further research on self-samples is warranted to find an optimal triage strategy. Until then, reflex cytology on self-samples could be easily implemented in the current screening programme and improve cervical cancer prevention.Diede L Loopik 1; Willem JG Melchers 2; Judith EM Vedder 3; Adriaan JC van den Brule4; Leon FAG Massuger 1; Ruud LM Bekkers5; Albert G Siebers 3,61 Department of Obstetrics and Gynaecology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, PO Box 9101, 6500HB, Nijmegen, the Netherlands;2 Department of Medical Microbiology, Radboud university medical center, PO Box 9101, 6500HB, Nijmegen, the Netherlands;3 Department of Pathology, Radboud university medical center, PO Box 9101, 6500HB, Nijmegen, the Netherlands;4 Department of Pathology, Lab for Molecular Diagnostics, Pathologie-DNA, Jeroen Bosch Hospital, PO Box 90153, 5200ME,‘s-Hertogenbosch, the Netherlands; 5 Department of Obstetrics and Gynaecology, Catharina Hospital, PO Box 1350, 5602ZA, Eindhoven, the Netherlands; 6 PALGA, the nationwide network and registry of histo- and cytopathology, Randhoeve 225a, 3995 GA, Houten, the NetherlandsPresent address Ruud LM Bekkers: GROW, School for Oncology & Developmental Biology, Maastricht University Medical Centre, PO Box 616, 6200MD, Maastricht, the Netherlands

Prostate cancer (PCa) is the second most common malignancy in men, and androgen deprivation therapy (ADT) is the first-line therapy. However, most cases will eventually develop into castration-resistant prostate cancer (CRPC) after ADT treatment. Enzalutamide (Enz) is a second-generation androgen receptor inhibitor approved by the Food and Drug Administration to treat patients with CRPC. Unfortunately, patients receiving Enz treatment will ultimately develop resistance via various complicated mechanisms. In this review, we introduce the emerging information on resistance mechanisms, including androgen receptor-related signalling pathways, glucocorticoid receptor-related pathways, and metabolic mechanisms. Notably, lineage plasticity and phenotype switching, gene polymorphisms, and the relationship between microRNAs and drug resistance are addressed. Furthermore, potential therapeutic strategies for Enz-resistant CRPC treatment are suggested, which can help in the discovery of more effective and specific regimens to overcome Enz resistance.

Nine slope runoff plots with different soil and water conservation measures were selected in Baima small watershed of Pingshun County, Shanxi Province of China, to explore more effective soil and water conservation measures to avoid soil nutrient losses, improve soil fertility, and control non-point source pollution. Soil organic carbon (SOC), total nitrogen (TN) and available potassium (AK) were determined and compared in this paper. The results show that,1) In grass measures, sowing of both riochloa is chaemum are more suitable for nutrient protection on the upper slope, fertility and the whole nutrient content of natural grass is optimum (SOC:24.86g/kg, TN:2.09g/kg, AK:157.00mg/kg);2) Plant combined with engineering measures ,in different plant measures(fish-scale pit), shrubs are more suitable for nutrient conservation on the upper slope. SOC (25.04g/kg) and TN (2.13g/kg) contents of coniferous trees were the highest, and AK (170.89mg/kg) content of broad-leaved trees was the highest;3) Plant combined with engineering measures ,among the different engineering measures(oriental arborvitae), the overall nutrient condition of level bench was the best (SOC: 33.33 g/kg, TN: 2.21 g/kg, AK: 139.44 mg/kg), and the stone dike terrace was poor (SOC: 18.19 g/kg, TN: 1.53 g/kg, AK: 118.11 mg/kg);4) The most suitable soil and water conservation measure was level bench of coniferous tree combine 9 measures. Soil nutrient contents are determined by plant characteristics, engineering measures and soil loss. In all plots, there were significant correlations between the three nutrients (P < 0.01), showing an strong effects of conservation measures on soil nutrients.

Background: The prognosis of children with acute myeloid leukemia (AML) has improved with the efficacy of hematopoietic cell transplantation as a second-line therapy and improvements in supportive care following anthracycline- and cytarabine-based chemotherapy; however, the outcomes of children with relapsed AML still remain unsatisfactory. Procedure: In order to identify prognostic factors and improve their prognosis, we analyzed 111 patients who relapsed after treatment with the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol and who were registered in the retrospective JPLSG AML-05R study. Results: The 5-year overall survival rate was 36.1%. The major determinant of survival was duration from the diagnosis to relapse. The mean duration in the non-surviving group (10.1 ± 4.1 months) was shorter than that in the surviving group (16.3 ± 8.3 months) (p<0.01). Moreover, achieving a second complete remission (CR2) prior to hematopoietic cell transplantation was associated with a good prognosis (p<0.01). Etoposide, cytarabine and mitoxantrone (ECM)- or fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG)-based regimens were therefore recommended for reinduction therapy (p<0.01). A genetic analysis also revealed the prognostic significance of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication as a poor prognostic marker (p=0.04) and core binding factor-AML, t(8;21) and inv(16), as good prognostic markers (p<0.01). Conclusions: Achieving a CR2 prior to HCT is important in order to improve the prognosis of relapsed pediatric AML. Recent molecular targeted therapies, such as FLT3 inhibitors, may contribute to overcome their prognoses. Larger prospective investigations are necessary to establish individualized treatment strategies for patients with relapsed childhood AML.

Objective: To establish a prediction model of clinical outcomes in women with placenta accreta spectrum (PAS) Design: Retrospective cohort study Setting: International multicenter study (PAS-ID); 11 centers from 9 countries Population: Women who were diagnosed with PAS and were managed in recruiting centers between January 1st, 2010 and December 31st, 2019. Methods: Data were collected using a standardized sheet, which included baseline information, medical and obstetric history, diagnosis, disease characteristics, management, and outcomes. Analysis of association between these variables and primary outcome was first conducted using conventional logistic regression. Data were reanalyzed using machine learning (ML) models, and 2 models were created to predict outcomes using antepartum and perioperative features. Main Outcome Measures: Massive PAS-associated perioperative blood loss (intraoperative blood loss ≥ 2500 ml, triggering massive transfusion protocol, or complicated by disseminated intravascular coagulopathy). Other outcomes include prolonged hospitalization > 7 days and admission to intensive care unit (ICU). Results: 727 women with PAS were included. Area under curve (AUC) for ML antepartum prediction model was 0.84, 0.81, and 0.82 for massive blood loss, prolonged hospitalization, and admission to ICU, respectively. Significant contributors to this model were parity, placental site, method of diagnosis and antepartum hemoglobin. Combing baseline and perioperative variables, ML model performed at 0.86, 0.90, and 0.86 for study outcomes, respectively. This model was most contributed by ethnicity, pelvic invasion, and uterine incision. Conclusions: ML models may be used to calculate individualized risk of morbidity in women with PAS, which may assist to outline management plan in priori

Background: As pregnancy is a physiological prothrombotic state, pregnant women may be at increased risk of developing coagulopathic and/or thromboembolic complications associated with COVID-19. Objectives: To investigate the occurrence of haemostatic and thrombo-embolic complications in pregnant women with COVID-19. Search Strategy: Two biomedical databases were searched between September 2019 and June 2020 for case reports and series of pregnant women with COVID-19. Additional registry cases known to the authors were included. Steps were taken to minimise duplicate patients. Selection criteria: Pregnant women with COVID-19 based either on a positive swab or high clinical suspicion e.g. symptoms and radiographic evidence. Data Collection and Analysis: Information on coagulopathy based on abnormal coagulation test results or clinical evidence of disseminated intravascular coagulation (DIC), and on arterial or venous thrombosis, were extracted using a standard form. If available, detailed laboratory results and information on maternal outcomes were analysed. Main Results: 1063 women met the inclusion criteria, of which three (0.28%) had arterial and/or venous thrombosis, seven (0.66%) had DIC, and a further three (0.28%) had coagulopathy without meeting the definition of DIC. Five hundred and thirty-seven women (56%) had been reported as having given birth and 426 (40%) as having an ongoing pregnancy. There were 17 (1.6%) maternal deaths in which DIC was reported as a factor in two. Conclusions: Our data suggests that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Detection of the former may be useful in the identification of women at risk of deterioration.

By doping two potassium atoms among three C20F20 cages, peanut-shaped single molecular solvated dielectron C20F20@K@C20F20@K@C20F20 as new type of spin molecular switches was theoretically presented. The triplet structure with two single-excess-electrons individually inside left and middle cages is thermodynamically more stable than the singlet one with lone pair of excess electrons inside middle cage. It is found that applying an oriented external electric field (OEEF) of 111 × 10-4 au (0.5705 V/Å) or -120 × 10-4 au (-0.6168 V/Å) in the x-axis direction firstly and then releasing it, the field-free triplet C20F20@K@C20F20@K@C20F20 with two single-excess-electrons can change into singlet one with lone pair of excess electrons through a singlet one with lone pair of excess electrons inside the end cage. Different spin states can bring significantly different dipole moment component values and considerable different intensities of maxumum wavelengths in intense absorption band. Therefore, C20F20@K@C20F20@K@C20F20 is a good candidate for spin molecular switching materials.

Objective To investigate the prevalence of vaginal flatus (VF) in women with pelvic floor disorders and its impact on quality of life. Design A cross-sectional study. Setting A tertiary medical center. Population Women visited a urogynecologic clinic in 2019. Methods Patients were asked about their experience of VF. Other evaluations included urodynamics, genital prolapse stage, and valid questionnaires, including the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), Urogenital Distress Inventory (UDI-6), and Incontinence Impact Questionnaire (IIQ-7). Clinical characteristics, urodynamic parameters, stage of prolapse, and quality of life scores were compared between women with and without VF. Main Outcome Measures: The impact of VF on quality of life. Results: Among 341 women, 118 (35%) reported VF, which was more common in those who were younger (49.3±9.2 vs. 59.9±13.4 yr, p<0.001) and more sexually active (98% vs. 55%, p<0.001) women. Women with VF had significantly worse sexual function (PISQ-12, 16.3±15.9 vs. 30.9±8.0, p<0.001), and incontinence-related quality of life (UDI-6, 23.4±10.5 vs. 17.8±8.9, p=0.039; IIQ-7, 25.5±14.5 vs. 17.2±12.5, p=0.012). For frequency and bother, 46% (48/116) of the women reported often or always having symptoms during sexual activity, 15% (5/34) when performing daily activities, and 12% (4/31) when exercising; and 60% (70/116) felt least moderate bothersome during sexual activity compared to 5% (2/34) when performing daily activities and 18% (6/31) when exercising. Conclusions: VF is prevalent in younger and sexually active urogynecologic patients. It has a significantly negative impact on sexual function. Routine counseling should be considered for these patients.

Paragangliomas (PGLs) are rare neuroendocrine tumors that arise from the autonomic ganglia. A 34-year-old woman was admitted to our department with palpitation, fatigue and chest pain under stress. Past medical history included a para-carotid PGL surgically removed 5 years earlier. Her family history was notable for familiar PGL with SDH mutation. At stress-echocardiography, was recorded a marked ST-elevation on precordial-leads, concomitant to new onset anterior septum hypo-kinesis, and therefore the patient was proposed for coronary angiography. Although angiographic evidence of atherosclerosis were not recorded, was found that Left Anterior Descending Coronary Artery gave off some branches towards a vascular structure (3×2 cm) in contiguity with the left coronary sinus of the aortic root. Subsequent Compute-Tomography and Magnetic-Resonance clarified the anatomical relationships of the mass with adjacent cardiac structures, in particular the mass was located behind the pulmonary artery trunk and lateral to aortic root, lying above the first portion of the anterior descending coronary artery. Subsequently a careful discussion about the risks and benefits of all therapeutic opportunity, the open surgical resection was deemed the best option for the patient despite the complex clinical anatomy. After standard cannulation for CPB and cardioplegic arrest, transection of the pulmonary artery and the aorta was performed granting adequate exposure of the mass and identification of afferent and efferent vascularization for complete resection though a cleavage plane. To ensure adequate hemostasis on a such critical area, the continuity of the pulmonary trunk was ensured only after removing aortic cross-clamp. The post-operative course was uneventful

Background and Aim of the Study: Barlow’s disease is characterized by excess myxomatous degenerative tissue, leaflets prolapse and/or billowing, chordal-elongation, and annular-dilation. We reviewed our experience in Minimally Invasive Mitral Valve Repair (MIMVR) techniques to treat this complex mitral pathology. Methods: Between 1999 and 2017 a group of 125 patients was identified as Barlow’s disease undergoing MIMVR. The diagnosis of Barlow disease was based upon preoperative transesophageal-echocardiography (TEE) and confirmed by the surgeon’s assessment during open-heart procedure. Operative technique and data were retrospectively collected along with intra-hospital and long-term follow-up. Results: Successful Mitral Repair was possible in 100% of cases (125 patents) within the first cross clamp. Most patients (118 – 94.4%) were treated by the Edge to Edge (Alfieri-Stich), while 2 (1.6%) where corrected by neochordae implant and 2 (1.6%) by quadrangular resection. 58 patients (47.1%) received complete semi-rigid ring, while 65 (52.9%) incomplete flexible partial ring excluding the LAM. Concomitant procedures were additional cleft occlusion in 10 cases (8%), tricuspid valve repair (ring implant or remodeling) in 29 cases (23.2%), left atrial ablation for atrial fibrillation in 4 cases (3.2%) and atrial septal repair in 4 (3.2%). Operative mortality was 0%. Average long-term follow-up was 85 ± 62 months, with a survival rate of 97.6%, freedom from redo mitral surgery of 98.4% and freedom from >2+ recurrent mitral regurgitation of 94.5%. No difference in outcome could be related to annuloplasty ring type. Conclusions: Mitral repair can be safely and successfully achieved though minimal-invasive approach, with optimal long-term results.

Linden and Yarnold1 recently proposed classification tree analysis (CTA), a machine‐learning procedure, as an alternative to conventional methods for analyzing mediation effects in treatment-outcome research. They note that CTA may have a number of advantages in this regard. It requires no assumptions about the distribution of variables or the functional form of the best-fitting model, for example, thus affording greater potential flexibility in identifying complex forms of association among variables with varying scales of measurement (e.g., binary and continuous). The authors further argue that CTA, unlike conventional approaches to testing mediation, “will not generate a model if a treatment-mediator-outcome relationship does not exist” (p. 359) and, conversely, that CTA “will systematically identify a treatment-by-mediator interaction if it exists, as well as any other interaction between variables.” (p. 359). Using data from the Job Search Intervention Study (JOBS II), they find that structural equation modeling, a conventional approach to testing mediation, failed to indicate support for job-search self-efficacy as a mediator of the effects of the intervention on whether the study participant was reemployed at follow-up. In contrast, the authors conclude that CTA applied to the same set of variables revealed that job-search self-efficacy was a mediator of intervention effects on employment among those in the treatment group.There are, however, two problematic aspects of the authors’ approach. First, as they point out, causal inference of a mediational pathway depends on the assumption that the associations involved exist net of potential confounding variables. In a randomized control trial such as JOBS II, confounding of the association between the mediator and outcome is of particular concern.2 The authors seek to address this concern by conducting a CTA that includes a set of 9 potential confounders (e.g., income, age, initial level of depressive symptoms) as candidate predictors. This approach does not ensure statistical control for these variables, however, for at least two reasons. First, there is no guarantee that the variables involved will actually be included in the resulting classification tree; failing to meet the criterion for inclusion does not rule out the possibility that a given potential confounder or combination of such confounders nonetheless share an association with the mediator and outcome to an extent that renders their association non-significant. This concern proves pertinent to the authors’ analysis as only 3 of the potential confounders earn entry into the resulting classification tree for reemployment status. A second concern with the approach taken by the authors is that whatever covariates are included in the classification tree may be included in positions that are inadequate for the purpose of controlling for confounding of the mediator-outcome association. Gender, for example, in their analysis is included in the control group branch of the tree, whereas job-search self-efficacy, the potential mediator, is included only in the treatment group arm. As a further example, education is included on the treatment group arm, but only after job-search self-efficacy’s role in the model already has already been established through its inclusion on a higher tier of the model. An alternative approach for addressing confounding in the context of CTA would be to residualize the candidate mediator on possible confounders and then fit a classification tree with this adjusted variable. If the residualized mediator continues to discriminate across levels of the outcome, conditional on treatment status, it could be concluded that the mediate-outcome portion of the potential mediational pathway of interest is evident independent of the measured confounders. Applying this approach, I find that the job-search self-efficacy continues to emerge as a discriminating variable for reemployment in the treatment arm branch of the classification tree that I fit with the same JOBS-II data. However, it cannot be assumed that this more rigorous approach to taking into account confounders will always yield the same result as one in which they are merely included as candidate predictors within a CTA.A more fundamental concern with the CTA approach to identifying mediation employed by the authors is that the mediator in the predictor-mediator and mediator-outcome segments of the mediational pathway are not assured of having a consistent definition. This is a result of the optimal cut-point on the mediator being determined separately for the two segments, through an optimal discriminant analysis for the treatment-mediator segment and CTA for the mediator-outcome segment. Thus, in the case of the mediational pathway for reemployment, treatment status predicts a dichotomous measure of job-search self-efficacy determined by a cut-score of 3.92 (i.e., high job-search self-efficacy corresponds to values above 3.92 and low to values equal to and below 3.92), whereas the dichotomous measure of job-search self-efficacy predicting reemployment is determined by a different cut-score of 4.92. Yet, it is essential by definition that the mediator in a mediational pathway that is influenced by the initial variable in the pathway (in this case, treatment) be the same variable that then influences the outcome (in this case, reemployment). In this case, nearly one half of the sample (47.3%; n = 426) has a different high-low classification on the job-search self-efficacy, suggesting considering divergence between the versions of this variable determined by the respective cut-scores. One approach to addressing this concern would be to define a new mediator that reflects the overlapping portion of the differing definitions. In the present example, this could be a dichotomous measure of job-search self-efficacy defined by a cut-score of greater 3.92, which would ensure that all those with scores classified as relatively high on the measure continue to be classified as such; alternatively, a cut-score of 4.92 could be used if priority is given to ensuring that all those classified as low remain in this category. Still another option would be to use the mid-point between the two cut-scores of 4.42. One could then evaluate the mediational pathway of interest using one or more of these options. Applying this approach using PROC CAUSALMED in SAS3, allowing for the suggested treatment-mediator interaction and including all covariates, I find evidence of an indirect mediated pathway when using the lower bound cut-off score of 3.92 for job-search self-efficacy (Odds Ratio for natural indirect effect of .959, 95% CI limits of .893, .998), but not when using the other two cut-off scores, although the differences in estimates are admittedly small in this case (complete results are available upon request).To summarize, Linden and Yarnold (2018) make a significant contribution by introducing CTA as a promising strategy for identifying mediated effects in intervention research. Further refinements to their approach, however, are recommended to more fully incorporate fundamental assumptions that accompany all tests for mediation as well as to evaluate and confirm potential mediational pathways using conventional procedures.References1Linden A, Yarnold PR. Identifying causal mechanisms in health care interventions using classification tree analysis. J Eval Clin Pract. 2018;24:353–361. https://doi.org/10.1111/jep.128482Imai K, Keele L, Tingley D. A general approach to causal mediation analysis. Psychol Methods . 2010;15:309‐334.3Yung, Y, Lamm, M, Zhang, W. Causal Mediation Analysis with the CAUSALMED Procedure . Paper SAS1991-2018. Cary, NC: SAS Institute Inc.; 2018.

Background, aims and objectives: With ageing global populations, hospitals need to adapt to ensure high quality hospital care for older inpatients. Older person friendly hospital (OPFH) principles and practices to improve care for older people are recognised, but many remain poorly implemented in practice. The aim of this study was to understand barriers and enablers to achieving OPFH from the perspective of key informants within an academic health system. Methods: Interpretive phenonomenological study, using open-ended interviews conducted by a single researcher with experienced clinicians, managers, academics and consumers who had peer-recognised interest in care of older people. Initial coding was guided by the Promoting Action on Research Implementation in Health Services (PARIHS) framework. Coding and charting was cross checked by three researchers, and themes validated by an expert reference group. Reporting was guided by COREQ guidelines. Results: Twenty interviews were completed (8 clinicians, 7 academics, 4 clinical managers, 1 consumer). Key elements of OPFH were: older people and their families are recognized and respected; skilled compassionate staff work in effective teams; and care models and environments support older people across the system. Valuing care of older people underpinned three other key enablers: empowering local leadership, investing in implementation and monitoring, and training and supporting a skilled workforce. Conclusions: Progress towards OPFH will require genuine partnerships between clinicians, consumers, health system managers, policy makers and academic organisations, and reframing the value of caring for older people in hospital.

Study of the soil water dynamic and water balance in coral islands is important to utilize and manage the limited freshwater resources of islands. In this study, we studied the soil water dynamic in Zhaoshu Island, Xisha archipelago using the observed data and the Richards equation, and analyzed the water balance of this island in the dry and wet seasons, respectively. The soil water movement showed that there was a dry soil layer at the depths between 40cm and 160cm of the soil profile in the dry season. The evaporation (Es) flux was low, but the transpiration (Er) could still absorb water from the capillary zone to maintain growth. In the wet season, the infiltration dominated the main process of soil water movement. The result of water balance showed the precipitation, the change values of water in the entire flow domain (△Volume), bottom boundary flux (vBot), Er, Es were 913mm, 10mm, 349mm, 203mm, 351mm, respectively from October 2018 to September 2019. Precipitation is the only source of the freshwater, about 38% of the precipitation infiltrated into the groundwater, 22% of the precipitation was uptaken by the vegetation, and 39% of the precipitation was evaporated from the land surface. In the dry season, the evapotranspiration (ETa) was just 44mm/month which was 94% larger than the precipitation, and about 14mm/month of water was uptaken from groundwater by the plants. But in the wet season, 56% of the precipitation infiltrated into the groundwater, 37% of the precipitation was consumed by ETa. This study can help us well understand the process of water movement in coral islands, and provide references for further management in protecting coral island ecologies.

Minimally Invasive Aortic Valve Replacement is not just a metric of the incision, but rather a holistic approach to minimize the surgical trauma: the technique should reproduce the gold-standard conventional procedure in terms of safety, effectiveness and operative times through a small and different incision. Moreover, the procedure should be simple and reproducible in every Center all over the world. In our experience, we rely more on surgical skills and technique optimization, rather than CT-scan planning: definitely, the pre-operative imaging is helpful in the beginning of the experience to rule out difficult cases.

To the Editor, Sweat conductivity (SC) is a well-established screening test for Cystic Fibrosis (CF).1,2 It is semi-automated, fast, doesn’t require skilled technicians or specialized personnel, and needs a small amount of sweat. Moreover, one response to the demanding and labour-intensive requirement for robust quality sweat testing has been the testing of sweat samples by electrical conductivity.3As every laboratory method, SC is subject to error. Then, it should be assessed and tested to ensure that it produces results which make it reliable and suitable for the intended purpose, i.e., its role as screening method. Repeatability is one of these vital requirements.The International Organization for Standardization defines repeatability as the nearest agreement between independent test results performed in identical conditions in a short period of time, i.e., same test items and steps, same equipment, same technician, same laboratory.4Although SC is adopted worldwide there is no study evaluating specifically that requirement in any age group, including newborns and young infants. Therefore, the present study aimed to assess the correlation between two concomitant SC assays.We prospectively and consecutively recruited clinically stable infants younger than 3 months. They had two previous positive immunoreactive trypsin results (IRT), and then, two concomitant SC assays, performed by the same technician in the same facility. IRT and SC were carried out in the single accredited Reference Center for Newborn Screening and Genetic Diagnosis, located in the city of Belo Horizonte, State of Minas Gerais, Brazil.Sweat samples were obtaining from each forearm through the Wescor Macroduct system and then analyzed through a SC analyzer (Sweat-Chek analyzer, model 3120, Wescor Inc., USA). All steps were performed according to the manufacturer’s recommendations, and described elsewhere.1,2Apart from descriptive statistics, to assess the relationship between the two SC assays we used Spearman’s rank correlation coefficient. SPSS software, version 18.0 (SPSS Inc., Chicago, Illinois) was used for statistical analyses. The research protocol was approved by the Research Ethics Committee of Federal University of Minas Gerais, under number CAAE 21958014.1.0000.5149.A total of 322 young infants were recruited. Most of them (89%) were from smaller towns within the same State, and 11% lived in Belo Horizonte, the State capital. There was a slightly predominance of males (54%), and the majority (59%) were younger than 60 days, being 15.2% of them aged up to 30 days of life. Mean and median age was 52 and 46 days (range, 19-89 days), respectively.A sufficient amount of sweat was obtained from all participants. Means and medians for the first and second SC values were 37.0 mmol/L, and 34.3 mmol/L (range, 29.0-39.6 mmol/L), and 38.0 mmol/L and 35.3 mmol/L (range 30.0-40.7), respectively.Figure 1 displays the Spearman’s correlation scatter plot for the two SC results.

Introduction: There is growing evidence that COVID-19 can cause cardiovascular complications. However, there are limited data on the characteristics and importance of atrial arrhythmia (AA) in patients hospitalized with COVID-19. Methods: Data from 1029 patients diagnosed with of COVID-19 and admitted to Columbia University Medical Center between March 1st and April 15th 2020 were analyzed. The diagnosis of AA was confirmed by 12 lead electrocardiographic recordings, 24-hour telemetry recordings and implantable device interrogations. Patients’ history, biomarkers and hospital course were reviewed. Outcomes of death, intubation and discharge were assessed. Results: Of 1029 patients, 82 (8%) were diagnosed with AA. Out of the 82 patients with AA. Of the AA patients, new-onset AA was seen in 46 (56%) patients, recurrent paroxysmal and chronic persistent were diagnosed in 16 (20%) and 20 (24%) individuals, respectively. Sixty-five percent of the patients diagnosed with AA (n=53) died. Patients diagnosed with AA had significantly higher mortality compared to those without AA (65% vs. 21%; p < 0.001). Predictors of mortality were older age (Odds Ratio (OR) =1.12, [95% Confidence Interval (CI), 1.04 to 1.22]); male gender (OR=6.4 [95% CI, 1.3 to 32]); azithromycin use (OR=13.4 [95% CI, 2.14 to 84]); and higher D-dimer levels (OR=2.8 [95% CI, 1.1 to7.3]). Conclusions: Patients diagnosed with AA had 3.1 times significant increase in mortality rate versus patients without diagnosis of AA in COVID-19 patients. Older age, male gender, azithromycin use and higher baseline D-dimer levels were predictors of mortality.

Instruction Cessation of oral anticoagulation (OAC) is common after the first 3 months of catheter ablation of atrial fibrillation (AF); however, thromboembolic risk has not been defined in patients with and without AF recurrence (RAF vs. NRAF) post ablationMethods and Results We identified 796 patients who discontinued OAC at 3 months post AF ablation from January 2015 to May 2018 in our center. Regular follow-up was performed to detect RAF, collect medication management and thromboembolic and major bleeding events. CHA2DS2-VASc score was 1.79±1.50; 547 (68.7%) patients were at intermediate and high risk (i.e. CHA2DS2-VASc score ³1 in male patients, or ³2 in female patients); 169 (21.2%) were RAF. During 29.2±12.2 months follow-up, the incidence rate of thromboembolism was 1.62 per 100 patient-year (7 in 431 years) in RAF, 0.33 per 100 patient-year (5 in 1503 years) in NRAF. After adjusting for potential confounding factors, RAF was associated with more 3.5-fold higher rate of thromboembolism compared with NRAF (adjusting HR, 4.488; 95%CI, 1.381-14.586). Rate of thromboembolism was even higher in patients with intermediate and high risk (2.16 per 100 patient-year [7 in 323 years] versus 0.38 per 100 patient-year [4 in 1043 years], aHR, 5.807; 95%CI, 1.631-20.671). In multivariate logistic regression analysis, RAF was the only independent predictor of thromboembolism (4.837 [1.498-15.621], P=0.008).