Elevation is involved in determining plant diversity in montane ecosystems. This study examined whether the species distribution of plants in the Yatsugatake Mountains, central Japan, substantiated hypotheses associated with an elevational diversity gradient. Species richness of trees, shrubs, herbs, ferns, and bryophytes was investigated in study plots established at 200-m elevational intervals from 1800 to 2800 m. The changes in plant diversity (alpha and beta diversities, plant functional types, and elevational ranges) with elevation were analyzed in relation to climatic factors and elevational diversity gradient hypotheses, that is, mass effect, mid-domain effect, and Rapoport’s elevational rule. A comparison of alpha and beta diversities revealed that different plant groups respond variably to elevation; the alpha diversity of trees and ferns decreased, that of herbs increased, whereas the alpha diversity of shrubs and bryophytes showed a U-shaped relationship and a hump-shaped pattern. The beta diversity of shrubs, herbs, and bryophytes increased above the subalpine–alpine transition ecotone. In accordance with these changes, the dominance of evergreen shrubs and graminoids increased above this ecotone, whereas that of evergreen trees and liverworts decreased. None of the plant groups showed a wide elevational range at higher elevations. These elevational patterns of plant groups were explained by climatic factors, and not by elevational diversity gradient hypotheses. These patterns were further influenced by plant–plant interactions via competition for light availability and physical habitat alternation.

Cardiac papillary fibroelastoma (CPF) is the most common valvular tumour of the heart and the second most common primary cardiac tumour. Fewer than 50 cases being reported in the literature [1]. As the advancement in 3D echocardiography, its diagnosis in living patient is become easy. The CPF could be found on valve leaflets, chordae tendineae, and both ventricles. We present an interesting case of the CPF originating from the posterior leaflet of the mitral valve confusing with vegetation or annular calcification. The patient underwent successful surgical removal of the PFE

Submission type: Correspondence and LettersAzacitidine as a bridge to allogeneic stem cell transplantation in a patient with juvenile myelomonocytic leukemia: a case reportAkira Takebayashi, MD1, Tsukasa Hori, MD, PhD1, Masaki Yamamoto, MD, PhD1, Takeshi Tsugawa, MD, PhD1, Keita Igarashi, MD1, Kotoe Iesato, MD, PhD1, Ryo Hamada, MD1, Hideki Muramatsu, MD, PhD2, Yukihiko Kawasaki, MD, PhD11Departments of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan2Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, JapanCorresponding author : Akira Takebayashi, MD, 291, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan. Phone: +81-11-611-2111; Fax: +81-11-611-0352; E-mail: take884akir@gmail.comKey Words : JMML, juvenile myelomonocytic leukemia, azacitidine, bridge, bridging therapy, stem cell transplantationRunning title : Azacitidine as a bridging therapy to JMMLWords count : 488 words, 1 table.Conflict of interest statement: The authors have no conflict of interest to declare.To the Editor:Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic /myeloproliferative neoplasm in infants and toddlers. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for most patients, but no appropriate pre-HSCT bridging therapy has been established. Since Furlan1 reported the effectiveness of azacitidine in pre-HSCT JMML, several reports have been published. Here we report a case of JMML treated with azacitidine.A 6-month-old male presented with hepatosplenomegaly and thrombocytopenia. Laboratory examinations revealed monocytosis (8.5 × 109 /L), mild anemia (hemoglobin: 10.2 g/dL), thrombocytopenia (17 × 109/L), and 11.7% hemoglobin F. Myeloblasts were peripheral blood: 2.0%; bone marrow: 8.2%. Fluorescence in situ hybridization detected monosomy-7 cells. Molecular analysis found a somatic KRAS p.G13D mutation, and he was diagnosed with JMML.We planned an unrelated bone marrow transplantation (UR-BMT) because an HLA-matched related donor was unavailable, and used 6-mercaptoprine (6-MP) as a bridging therapy. However, he still needed frequent transfusions and his hepatosplenomegaly was exacerbated (TABLE 1). We therefore changed the bridging therapy from 6-MP to azacitidine (2.5 mg/kg, over 1 hour intravenously on 7 consecutive days, every 28 days; TABLE 1). Platelet transfusion frequency decreased and he became transfusion-independent after azacitidine Cycle 6. Peripheral blood myeloblasts disappeared after Cycle 6, and the hepatosplenomegaly had completely improved after Cycle 8. Monosomy-7 cells significantly decreased, but did not disappear until his UR-BMT. He maintained clinical partial remission and genetic stable disease after Cycle 1, evaluated with response criteria defined by C. M. Niemeyer et al. Adverse effects of azacitidine included febrile neutropenia after Cycle 1 and exacerbated thrombocytopenia during Cycles 1 and 2. However, he suffered no adverse effects after Cycle 3.UR-BMT from an HLA 7/8 matched donor was performed after azacitidine Cycle 8, when the patient was in partial remission. His conditioning regimen included busulfan, fludarabine and melphalan; a short course of methotrexate and tacrolimus was used as prophylaxis against for graft-versus-host disease. He remains in complete remission with complete donor chimerism at 27 months after UR-BMT.Azacitidine is a DNA-hypomethylating agent used for myelodysplastic syndrome in adults, but is not generally used for JMML. Cseh reported twelve patients with JMML treated with azacitidine,3of whom nine patients were treated with azacitidine before HSCT and five achieved partial or complete remission. The remaining four received HSCT during progressive disease after 1–4 cycles of azacitidine therapy. Although the optimal number of azacitidine cycles is unknown, continuing azacitidine therapy for six to eight cycles might be valuable if the patient can tolerate it.Another infant with JMML, somatic KRAS mutation and monosomy-7 who achieved sustained remission following azacitidine monotherapy had been reported,4 but identifying patients who can sustain remission without HSCT is not currently possible. Reportedly, DNA methylation patterns in JMML can be predictive for prognosis,5,6 but whether they can predict response to hypomethylating agents or not is unclear. Although azacitidine bridging therapy is effective for JMML patients, further studies are needed to clarify several questions about JMML treatment.

Careful physical examination of the site of procedure before the caudal pain procedure should be performed because it could show the patient's abnormal anatomical conditions. An abdominal binder could be used effectively in a patient showing CSF leakage in the coccygeal area, which is not controlled by conventional compressive dressing.

Background: The incidence of allergic diseases has been rising in the last decades. The interplay between genetic and environmental factors underlined these complex diseases. Data concerning natural history and risk factors associated with allergic diseases in developing Asian countries are limited. Methods: A population-based birth cohort study was conducted in Bangkok, Thailand. Perinatal and postnatal factors were prospectively collected by questionnaires. Sensitization was identified by skin prick test. Food allergy (FA) was confirmed by oral food challenge. Results: A total of 369 mother-children pairs were enrolled and follow-up until the age of 30 months. The cumulative incidence of allergic diseases was 46.2%. High family income significantly increased risk of atopic dermatitis (AD) and ever-wheezing. Maternal history of allergic diseases and exclusive breastfeeding longer than six months significantly increased risk of FA. Antibiotics use in infants significantly associated with FA, ever-wheezing and rhinitis. Infants with FA had a 6.5-fold increased risk of AD while infants with AD had an 8.5-fold increased risk of FA. AR had a 3.5-fold increased risk in developing ever-wheezing. One-third of the subjects had aeroallergen sensitization. Conclusion: Prevalence of allergic diseases in developing Asian country was considerably high. AD and FA were the most prevalent allergic diseases during the first years of life. Meanwhile, the prevalence of wheezing and rhinitis subsequently increased over time. High sensitization rate to aeroallergens was found in the first two years of life. Maternal atopy, high family income, early life exposure to antibiotics and prolonged breast-feeding increased risk of allergic diseases in our cohort.

Iterative learning control (ILC) offers an effective learning control scheme to solve the control problems of the batch processes. Although the control performances of ILC systems can be improved batch-by-batch, the convergence still strongly depends on the repeatability of the process and thus lack of robustness. Meanwhile, the data-driven-based deep reinforcement learning (DRL) algorithms have good robustness due to the generalization of the neural network, but it has lower data efficiency in training. In this paper, we propose a complementary control scheme for the batch processes by employing a DRL guided by a classical ILC, termed as the IL-RLC scheme. This scheme has higher data efficiency than the DRL without guidance and better robustness than the ILC, which are demonstrated by the numerical simulations on a linear batch process and a nonlinear batch reactor. This work provides a way for the application of DRL algorithm in the batch process control.

Rhizosphere fungi are essential for plant survival and ecosystem functioning, but the processes structuring plant-fungal interactions remain largely unknown. We constructed association networks between 43 plant species and two groups of root-associated fungi (mycorrhizal and pathogenic) using sequence data. We revealed modularity within the association networks using network analysis, and correlated this modular structure with functional traits and phylogenetic history driving plant-fungal interactions. We observed strong modularity in both plant-mycorrhizal fungal and plant-pathogenic fungal association networks. Plant functional traits and fungal phylogeny clustered within modules. Host plants of mycorrhizal fungi differed significantly between modules in terms of their leaf dry matter content, photosynthetic traits and root tissue density. Host plants of pathogenic fungi differed significantly between modules in terms of their dark respiration rate, light compensation point and root morphology. Modularity within fungi was a product of fungal phylogeny, whereas host plant modularity was a product of functional traits (leaf morphology, photosynthetic rate and root morphology). Our study illustrates the link between plant functional traits and fungal assembly, and highlights the importance of niche-based processes in shaping plant-fungus association networks. Our results suggest that plant traits may be instrumental in managing the composition of belowground fungal communities.

Obesity and non-alcoholic fatty liver disease (NAFLD) are “lifestyle diseases” related to harmful habits, affecting a large portion of the global population at a steadily increasing prevalence. These disorders are inextricably associated with each other and therapeutic lifestyle changes (TLC) remain the cornerstone of their management. Nevertheless, TLC are difficult to achieve or maintain, and the use of medicines is often suggested. Different categories of medicines have been proposed, many of which are not officially licensed for these conditions. For NAFLD in particular, no drug with official indication exists so far. Thus, it is important that clinicians are aware of the quality of evidence supporting the efficacy of drugs before a decision to treat. To assist rational medical decision, in the present systematic review, we sought to evaluate the quality of evidence from phase III/IV clinical trials of major drugs currently proposed for obesity and NAFLD.

Coronavirus disease2019(COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. Therefore, for COVID-19 patients, Convalescent plasma, could prove lifesaving, such as improving the clinical symptoms, increasing the neutralizing antibody, decreasing the viral load , reducing the death rate, with safety and without seriously ADE. Meanwhile, it is urgent to perform large sample randomized controlled trials to confirm the transfusion timing, dosage, frequency and actively prevent adverse outcomes that may occur, establishing a standard procedure for treatment from convalescent plasma collection, preservation, transport, to transfusion.

Background and Purpose: Humans have been fighting vitiligo for centuries but still being inferior due to the lack of efficiency drugs and therapies. While some research has implied the therapeutic potential of Wnt/β-catenin signalling on curing vitiligo but correlation mechanism is not clear and no Wnt-specific anti-vitiligo drug has been reported. Here, We identified how vitiligo could be treated by regulating Wnt and two lead compounds of new anti-vitiligo drugs have been found. Experimental Approach: Wnt agonists were rational synthesized and then be evaluated their effects on vitiligo in B16 cells and C57B/L mouse. Furthermore, Co-IP and Site-directed mutagenesis were employed to indicate the mechanism and the target of the compounds. Key Results: HCJA121 and HCJA404 could significantly promote the synthesis of melanin, restore the pigmented function of skin, and improve the symptoms of vitiligo. Mechanism studies indicated that HCJA121 and HCJA404 target the DAX domain of Axin by binding to LYS781 and LEU784 then potentiate the Axin-LRP6 association and eventually promoted melanogenesis. Conclusions and Implications: These findings imply an alternative regulatory mechanism of melanogenesis and the Axin protein could be a new target for anti-vitiligo agents which reveal a therapeutic strategy for vitiligo. Besides, HCJA121 and HCJA404 may represent potential compounds for vitiligo treatment.

Introduction Autologous fat grafting (AFG) has both aesthetic and reconstructive applications. Described by Neuber in 1893 there are numerous applications of AFG as the body of evidence for its use has expanded. The earliest controversies were evident in lipofilling for breast defects post-oncological treatment, and to this day some countries do not allow it for fear of inducing tumourogenesis in an oncologically ablated field. Adipose-derived stem cells (ASCs) have been shown pro-oncologic behaviour in xenografts, however, this has not been reproduced in clinical observations thus far. Material and Methods We sought to review contemporary harvesting and processing techniques for AFG in the craniofacial region, therefore distributed a survey to evaluate the opinion and clinical impact of oncological risk across four European countries with possibly differing clinical attitudes.  Results In the craniofacial region AFG is mostly used for aesthetic indications, cannula hand-held aspiration and centrifugation seem to be the predominant harvesting and processing techniques. Half of our respondents tell patients about the possibility of pro-oncologic behaviour of AFG. We found no significant geographical differences between the German-speaking and the English groups concerning their harvesting and processing technique. German participants seem to perform AFG more often and mostly use it for cosmetic and post-cancer treatment sequelae, English participants homogenically use AFG for cosmetic reasons.Conclusion Theoretical pro-oncologic behaviour of craniofacial AFG does not deter surgeons. Perhaps, we shouldn’t consider discussing this complex area of oncogenesis with patients as there is no elevated risk from what we know.

Avian influenza (AI) is a contagious disease of birds with zoonotic potential. AI virus (AIV) can infect most bird species, but clinical signs and mortality vary. Assessing the distribution and factors affecting AI incidence can direct targeted surveillance to areas at risk of disease outbreaks, or help identify disease hotspots or areas with inadequate surveillance. Using virus surveillance data from passive and active AIV wild bird surveillance, 20062020, we investigated the association between a range of landscape factors and game bird release and the presence of AIV. Furthermore, we assessed potential bias in the passive AIV surveillance data submitted by the public, via factors related to public accessibility. Lastly, we tested the AIV data for possible hot and cold spots within Denmark. The passive surveillance data was biased regarding accessibility to areas (distance to roads, cities and coast) compared to random locations within Denmark. We found significant effects of variables related to coast, wetlands and cities for the passive and active AIV surveillance data (P< 0.01), but found no significant effect of game bird release. We used these variables to predict the risk of AIV presence throughout Denmark, and found high-risk areas concentrated along the coast and fjords. For both passive and active surveillance data, low-risk clusters were mainly seen in Jutland and northern Zealand, whereas high-risk clusters were found in Jutland, Zealand, Funen and the southern Isles such as Lolland and Falster. Our results suggest that landscape affects AIV presence, as coastal areas and wetlands attract waterfowl and migrating birds and therefore might increase the potential for AIV transmission. These findings have enabled us to create risk maps of AIV incidence in wild birds and pinpoint high-risk clusters within Denmark. This will aid targeted surveillance efforts within Denmark and potentially aid in planning the location of future poultry farms.

Coronaviruses (CoVs) are a well-known cause of severe enteric, respiratory, and systemic disease in a wide range of animals and in humans. To understand the route of disease origin and viral transmission in companion animals, a comparative pan-genomic analysis of coronavirus sequences originating from major felines and canines were conducted. The average nucleotide identity (ANI) is a rapid procedure for assessing the very close antigenic relationship between feline CoV (FCoVs) and canine CoV (CCoVs) and ANI-based phylogenetic tree that clustered CoVs according to their respective host species. While pan-genomic analysis demarcated strains clearly. The distribution of the clinical isolates all across the categories in the hierarchical phylogenetic model enabled the visualization of their original ecological niche rather than their isolation source, as infections are extremely rare events and evolutionary dead-ends. In polymorphism analysis, we found seven accessory gene clusters common to the FCoV/CCoV category clade, including pantropic strains, that perform functions supporting their pathogenicity. In addition, the gene presence/absence among FCoVs and CCoVs would provide very valuable information on species-specific control measures against CoV disease, such as the selection of good markers for differentiating new species from common and/or pantropic isolates. Also, the virulent FCoV strains were grouped with human CoV strains NL63 and 229E confirming hypotheses stating that cats are highly susceptible to HCoVs, while dogs have low susceptibility to the virus. In conclusion, the combined analysis allows for better phylogenetic resolution and the implication of virus origins, recombination, and virus–host interaction, as well as biomarkers.

A case of a severe paravalvular mechanical mitral prosthesis leak in a high-risk patient that underwent previously 4 mitral valve surgeries is described. An Amulet-Amplatzer device was correctly implanted on the left atrial appendage, with the temptative to close also the contiguous severe leak. A residual moderate paravalvular leak caused acute hemolysis with severe renal failure requiring hemodialysis. The transesophageal echocardiogram is crucial in localizing and defining the extent of the paravalvular leak. It is not clear if the hemolysis was precipitated by the evolution of the disease or by the residual regurgitation after Amulet device deployment. Certainly, given the intricacy of the procedure the results might be limited also for highly expert operators. To our knowledge, this is the first case reporting the use of the Amulet-Amplatzer device for paravalvular leak closure.

Key points: • Intraoral, sublabial, and transnasal endoscopic approachs are used to manage odontogenic maxillary cysts. • Transnasal endoscopic approach includes inferior meatal antrostomy, middle meatal antrostomy, and endoscopic medial maxillectomy approach. • Trans-antral endoscopic assisted excision of odontogenic maxillary cyst approach have the advantage of direct lesion access of the sublabial approach as well as the advantages of better illumination, magnification, and small access of endoscopic approach. • The trans-antral endoscopic assisted approach co-morbitity seems to be the least comparing to the benefit of complete excision of the cyst within its entire wall in all the cases with minimal injury of the unaffected maxillary sinus mucosa as well as avoidance of injury of any nearby structure if there is defect in the sinus wall.

La rimozione di contaminanti ambientali dal nostro sistema idrico continua ad essere prioritaria, in quanto tali sostanze hanno impatti negativi sull’ambiente e sulla salute umana. Tra le tecniche più diffuse per la rimozione di materia organica presente nelle acque reflue, vi sono i processi di ossidazione avanzata, ed in particolare l’adsorbimento mediante carbone attivo granulare.  Studi recenti hanno scoperto come l’utilizzo di processi ad ultrasuoni (US) migliori l’adsorbimento per molti contaminanti ambientali. Nel presente lavoro vengono descritte le indagini condotte per esaminare e valutare l’efficacia del processo di adsorbimento del fenolo, scelto come indicatore di materia organica, mediante carbone attivo granulare (GAC), in assenza e in presenza di ultrasuoni. I risultati ottenuti dimostrano come l’utilizzo combinato di carbone attivo granulare e di ultrasuoni migliori l’adsorbimento del fenolo, in quanto garantisce un tasso di adsorbimento più elevato e una maggiore rimozione della sostanza organica. Ulteriori sviluppi scientifici, inoltre, danno conferma di come l’impiego di irradiazioni ultrasoniche combinate con l’azione del carbone attivo granulare, e con diverse tecnologie, migliori drasticamente la rimozione di contaminanti ambientali dalle acque reflue, garantendone la depurazione e il riutilizzo.

Background: There is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43–1.22, p=0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89–1.46, p=0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI. Conclusions: This trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629)

A document by Jaclyn McAlees. Click on the document to view its contents.

Background. Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods. We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results. ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion. Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.

Objectives We aimed to summarize the clinical presentations, therapeutic approaches, and outcomes of type B intramural hematoma (IMHB) patients with and without type 2 diabetes mellitus (DM). Methods Patients with uncomplicated IMHBs were included between January 2016 and January 2018 and divided into two groups according to whether or not they had DM. Cox proportional hazard analysis was utilized to investigate the risk factors for aortic-related mortality. Kaplan-Meier survival analysis was used to estimate cumulative mortality and aortic-related mortality. Results A total of 149 patients were included and were divided into the two groups (DM group [n=60] and non-DM group [n=89]). Patients in the non-DM group underwent thoracic endovascular aortic repair treatment more frequently (12% vs 2%, P=0.028) and had a higher reintervention rate during the follow-up (9 in 81 patients, 11% vs 2%, P=0.043). There were significant differences between the two groups regarding the aorta-related mortality rate during the acute phase (9% vs 0%, P=0.042) and the all-cause mortality rate (22% vs 7%, P=0.011). Ulcer-like projection (ULP) development (during the acute phase) (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.01-1.31, P=0.008), C-reactive protein (CRP) levels (HR, 1.92; 95% CI, 1.51-2.49, P<0.001) and MMP-9 levels (HR, 16.82; 95% CI, 7.52-28.71, P<0.001) were associated with an elevated risk for aorta-related mortality. Conclusions IMHBs without DM are not benign and have a considerably high aortic-related mortality rate. ULP development (during the acute phase), CRP levels and maximum MMP-9 levels are associated with an elevated risk for aorta-related mortality.

Ventricular septal rupture (VSR) is a life-threatening complication of trans-mural acute myocardial infarction (MI). Surgical intervention remains the treatment of choice, but it is still a challenging operation associated with high mortality (1). VSR is a rare serious complication of MI. Its incidence has been estimated between 1%¬ - 2% after MI. If it treated medically the mortality is very high (25% in 1st day, 75% at 1st week and 90% at 2 months). Patients that survive following medical treatment usually have clinically poor cardiac function. So, the result of medical treatment of VSR is disappointing (2). Primary PCI following MI can be significantly reduced the incidence of mechanical complications. However, with improving treatment, appropriate management of mechanical complications remains a cornerstone to avoid low cardiac output (LCO) and multi organ failure (MOF). Medical treatment has high failure and mortality rate, and early surgical ventricular septal defect (VSD) closure is recommended to reverse the hemodynamic deterioration. However, surgical repair is associated to a high rate of mortality (20% –40%) even in the more recent reports (3). Transcatheter device closure of VSR, is an option, however it is generally accepted to be inadequate. Progressive deterioration in hemodynamic status makes surgical intervention often the only realistic option (4).

Background and aim of the study This study aims to provide an overview of clinical outcome after bioprosthetic aortic root replacement and lifetime event-risk estimates of mortality and valve-related events, and the potential effect of type of prosthesis used. Methods A systematic literature search was conducted between January 2000 and August 2019. Inclusion criteria: aortic root replacement in adults. Data were pooled by inverse-variance weighting and entered a microsimulation model to calculate lifetime event-risk and (event-free) life expectancy. Results Of 2.106 publications, 31 were included (N = 5.227 patients, 74% stentless valves). Mean age was 65.4 years (74% male). Pooled early mortality was 5.5% (95% CI: 4.3-7.2%). During follow-up (mean 4.1 years, total 22.706 patient-years), late mortality was 4.8%/patient-year and reoperation 0.9%/patient-year. Linearized-occurrence-rates for thromboembolism, endocarditis, and hemorrhagic events:1.2; 0.9 and 0.5 %/patient-year; no significant difference between stented and stentless prosthesis. Translating into a 60-year-old patient, an estimated life expectancy of 14 years (general population: 22 years) and lifetime risks of thromboembolism, endocarditis and reintervention of 21%, 13%, and 8%, respectively is expected. Conclusions The study shows impaired survival and a notable lifetime risk of valve-related events after bioprosthetic aortic root replacement. The risk of thromboembolism is prominent, especially during earlier follow-up, suggesting higher risk of thromboembolism early after operation. Type of prosthesis, stented or stentless, is not associated with higher valve-related events. Moreover, this study could be used as a benchmark to compare outcome with other aortic root replacement procedures.

Pollinator foraging behavior determines floral visitation rates, an important proxy to the strength of mutual- istic interactions. Although there is evidence that pollinators modify their behavior in the presence of other foragers, there are equivocal findings regarding whether or not pollinators interfere with one another. We employ a functional-response framework to analyse experimental data of times between floral visits made by a focal pollinator and to estimate pollinator interference by conspecifics and three other species. Additionally we develop and compare models that allow different levels of resource availability and the sub-lethal exposure to a neonicotinoid pesticide to modify how pollinators forage alone and with co-foragers. We found that all co-foragers interfere with a focal pollinator under at least one set of abiotic conditions; for most species, interference was strongest at higher levels of resource availability and with pesticide exposure. Overall our results highlight that density-dependent responses are often context dependent themselves.

Purpose: The aim of this study is to determine the problems occurring during the COVID-19 pandemic period in patients treated with intravitreal (IV) injection for diabetic retinopathy, and to provide recommendations for treatment management in these patients. Methods: Twenty-nine eyes of 17 patients were included in this prospective, observational study. The frequency of hospital visits, treatments performed, and detailed ophthalmological examination findings, including optical coherence tomography findings and glycated haemoglobin (HbA1c) values, were recorded in the period before the COVID-19 pandemic. During the COVID-19 pandemic period, the detailed ophthalmological examination findings and HbA1c values were noted after the patients who had delayed their routine control time (>90 days) applied to the hospital. New treatments were planned according to the current situation. Results: Seventeen patients who were diagnosed with diabetic macular edema were included in the study; 10 were female (58.8%) and seven were male (41.2%). The mean time interval between following visits was 45.52±5.85 days during the pre-pandemic period, but it increased to 110.41±13.47 days during the COVID-19 pandemic period (p<.001). Visual acuity (LogMAR) was 0.44±0.36 in the pre-pandemic period and 0.76±0.48 during the COVID-19 pandemic period (p=.003). Central macular thickness was 300.10±85.56 µm in the pre-pandemic period and it increased to 387.10±144.48 µm during the COVID-19 pandemic period (p=.007). In three patients, complications of diabetic retinopathy that could not be cured by medical treatment developed and surgical treatment was recommended. Conclusions: Delays in the treatment of diabetic retinopathy may cause permanent impairment in visual functions. The COVID-19 pandemic has caused an increase in the hospital visit intervals of patients, and this situation has resulted in disruptions in the follow-up and treatment of patients with diabetic retinopathy. Alternative diagnosis and treatment practices are needed in order to manage these and similar processes smoothly.