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Onursal Sağlam

and 9 more

Abstract Background: As WHO expresses, COVID-19 is the infectious disease caused by the most recently discovered coronavirus. This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. COVID-19 is now a pandemic affecting many countries globally. Antiviral agents play fundamental role in Covid-19 treatment. Favipiravir is one of the favored agents and it still draws attention of generic drug industry which is constitutional for drug accessibility. Objective: The aim of this study is to demonstrate the bioequivalence of a new Favipiravir tablet formulation as compared to the reference tablet formulation in healthy male subjects under fasting conditions.To prove the bioequivalence, a randomised, single oral dose, cross-over, two-period study was carried out in 30 healthy subjects under fasting conditions. Plasma Favipiravir levels were quantified by using an in-house-developed high performance Liquid Chromatography Coupled to Tandem Mass Spectrometry (LC-MS/MS) method. Results: The 90% CIs for the test/reference geometric mean ratios of the Cmax and AUC0-tlast were 92.92 – 119.89% and 94.00 – 99.77%, respectively. Conclusions: This single-dose study has shown that the test and reference Favipiravir products met the required bioequivalence criteria. Besides, both products were well tolerated and safe. *The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions.

Pauline Blin

and 14 more

Invasive pathogens can be a threat when they affect human health, food production or ecosystem services, by displacing resident species, and we need to understand the cause of their establishment. We studied the patterns and causes of the establishment of the pathogen Dickeya solani that recently invaded potato agrosystems in Europe by assessing its invasion dynamics and its competitive ability against the closely-related resident D. dianthicola species. Epidemiological records over one decade in France revealed the establishment of D. solani and the maintenance of the resident D. dianthicola in potato fields exhibiting blackleg symptoms. Using experimentations, we showed that D. dianthicola caused a higher symptom incidence on aerial parts of potato plants than D. solani, while D. solani was more aggressive on tubers (i.e. with more severe symptoms). In co-infection assays, D. dianthicola outcompeted D. solani in aerial parts, while the two species co-existed in tubers. A comparison of 76 D. solani genomes (56 of which having been sequenced here) revealed balanced frequencies of two previously uncharacterized alleles, VfmBPro and VfmBSer, at the vfmB virulence gene. Experimental inoculations showed that the VfmBSer population was more aggressive on tubers while the VfmBPro population outcompeted the VfmBSer population in stem lesions, suggesting an important role of the vfmB virulence gene in the ecology of the pathogens. This study thus brings novel insights allowing a better understanding of the pattern and causes of the D.solani invasion into potato production agrosystems, and the reasons why the endemic D.dianthicola nevertheless persisted.

Yu-Jih Su

and 1 more

Objective. Biologics have been linked to both anti-autoimmune and anti-inflammatory mechanisms. We examine the long-term effects of biologics on rheumatoid arthritis (RA) patients in a real-world analytic cohort study using a nationwide database. Design. We designed a cohort study using the National Health Insurance Research Database in Taiwan between 1997 and 2010. Methods. Based on biologics and other anti-rheumatic agent prescriptions, we divided all patients into either the biologics group or the non-biologics group. The outcomes were the incidence rate of each comorbidity and the hazard ratio of each comorbidity between those using biologics and those not. We followed patients from the index date to the date on which the database ended. Results. In total, 19,681 patients were eligible for analysis in this study. During an average follow-up of 15 years, the event rates of each comorbidity differed significantly between the users and non-users of biologics with regard to cardiovascular comorbidity, metabolic comorbidity, rheumatologic comorbidity, and the miscellaneous comorbidity (all p<0.05). The usage of biologic agents in RA patients reduced the HR of cardiovascular comorbidities by 18%, metabolic comorbidities by 17%, rheumatology comorbidities by 36%, and miscellaneous comorbidities by 15% compared to those patients who did not use biologics. Oncology comorbidities and infection comorbidities were not affected by treatment with biologics (p>0.05). Conclusions. Biologics may have benefits beyond arthritis control with regard to reducing real-world comorbidities.

Tamaki Nakamura

and 10 more

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE cell-mediated food allergy characterized by repetitive vomiting and other gastrointestinal symptoms. Although little is known about FPIES pathophysiology, some cytokines have been reported to be involved. Since one of the main symptoms is vomiting, which is common to other diseases, it is difficult to distinguish acute FPIES from other conditions such as infectious enterocolitis. Thus, specific biomarkers are required for differential diagnosis. We aimed to identify potential biomarkers distinguishing acute FPIES from infectious enterocolitis and IgE-mediated anaphylaxis, which also cause vomiting. Methods: Seven patients with acute FPIES, nine with IgE-mediated anaphylaxis, and six with infectious enterocolitis were enrolled. The serum concentrations of interleukins (IL)-2, -4, -6, -8, -10, interferon-γ, and tumor necrosis factor-α were measured and compared among the three groups of patients. The serum concentrations of IL-2 and IL-10 were also compared between the symptomatic and asymptomatic stages. Alterations in serum cytokine levels were evaluated in acute FPIES during an oral food challenge test. Results: Serum IL-2 and IL-10 levels were significantly higher in acute FPIES patients than in patients with infectious enterocolitis and IgE-mediated anaphylaxis, whereas no significant differences were detectable in the serum levels of the other cytokines. The IL-2 and IL-10 elevation was only observed in the symptomatic stage of acute FPIES. Conclusion: The elevation in serum levels of IL-2 and IL-10 was specifically observed in symptomatic acute FPIES cases, suggesting that the measurement of IL-2 and IL-10 could be employed for differential diagnosis.

Stefania Arasi

and 14 more

Background: Allergen immunotherapy(AIT) is the only disease-modifying treatment with long-term effects in patients with seasonal allergic rhinoconjunctivitis(SAR). Its efficacy depends on the precise identification of the pollen triggering symptoms. However, a diagnostic approach based on retrospective clinical history and sensitization to extracts often does not lead to unequivocal results. Objectives: To assess the usability and impact of a recently established algorithm for a potential clinical decision support system (@IT.2020-DSS) for pollen allergy and its diagnostic steps (including anamnesis, SPT, component resolved diagnosis, CRD, and real-time digital symptom recording, eDiary) on doctor’s AIT prescription decisions. Methods: After a concise educational training on the @IT.2020-DSS algorithm, 46 doctors (18allergy specialists, AS, and 28general practitioners, GP) expressed their hypothetical AIT prescription for 10 clinical index cases. Decisions were recorded repeatedly based on different steps of the support algorithm. The usability and perceived impact of the algorithm on individual clinical performance were evaluated. Results: The combined use of CRD and an eDiary increased the hypothetical AIT prescriptions, both among AS and GP (p<.01). AIT prescription based on anamnesis and SPT were heterogeneous but converged towards a consensus after the integration of CRD and eDiary information. Doctors considered the algorithm useful and recognized its potential in enhancing traditional diagnostics. Conclusions: The implementation of CRD and eDiary in the @IT2020-DSS algorithm improved consensus on hypothetical AIT prescription for SAR among AS and GP. The hypothesis, that a CDSS for etiological SAR diagnosis and AIT prescription may be useful in real-life clinical practice deserves further investigations.

chaonan Zhao

and 5 more

Wind erosion is the main form of soil erosion in arid and semi-arid areas. It leads to soil loss and land degradation, which aggravates ecosystem vulnerability and threatens regional sustainable development. The assessment of wind erosion and the study of its driving factors can reduce soil wind erosion and provide decision-making assistance to solve environmental problems. Southern Africa is affected by severe soil erosion, which has brought a series of development problems, such as food crises and poverty. This study used meteorological and remote sensing data, and the revised wind erosion equation model to explore the temporal and spatial dynamics of soil erosion in southern Africa from 1991 to 2015. The impact of climate dynamics on soil wind erosion was also analyzed. The results showed that wind erosion fluctuated during the study period, and it first showed a downward trend and then stabilized at a relatively low level after 2010. Soil wind erosion across 66.65% of the study area significantly decreased (p < 0.05) and near-surface wind speed was the most important factor. The change in wind speed had a positive impact on soil wind erosion across 68.18% of the area. Temperature and precipitation were significantly related to soil wind erosion over 18.96% and 24.63% of the area, respectively. Both can also indirectly affect soil wind erosion through their effects on vegetation cover. This study will help decision-makers to evaluate areas that are at high-risk from soil erosion in southern Africa and enable them to effectively protect fragile ecosystems.
No abstract - Ist paragraph of the article A species’ ecological significance remains same whether it is found inside or outside a protected area (PA) then why the PAs are obligatory guarantor to maintain the biodiversity within their boundaries (Gascon et al. 2015)? Despite an increase in the number of PAs, connectivity is generally poor between and amongst the PAs, over 60% of PAs are too small to support major ecologically important and migratory species and eventually biodiversity is falling across the board (Coad et al. 2019). The PA approach, which was developed in the 20th century has been widely recognised as one of the most important strategies for achieving conservation goals (Shafer 2015). However, in the 21st century, it appears that PA based conservation approach has almost reached its practical and political limits (Coad et al. 2019; Shafer 2015) . Over the previous 1.5 century, the role of PAs was explored and expanded and both success and failures have been spectacular(Shafer 2015; Kalamandeen & Gillson 2007; Butchart et al. 2010; Watson et al. 2014). Most of the PAs were established for the primary goal of conservation and later sustainable growth have now stretched to contribute towards livelihood, poverty reduction and national development (Shafer 2015). Over 202,000 PAs worldwide, cover almost 15% of planet’s surface under some practice of protection (Terraube et al. 2020). Moreover, substantial wildlife exists outside the PAs, where exact estimates are not available due to insufficient monitoring efforts (Cox & Underwood 2011; McCleery et al. 2020).

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Recently published in scholarly journals

Wahaj Munir

and 3 more

Background: Acute type A aortic dissection (ATAAD), is a surgical emergency often requiring intervention on the aortic root. There is much controversy regarding root management; aggressively pursuing a root replacement, versus more conservative approaches to preserve native structures. Methods: Electronic database search we performed through PubMed, Embase, SCOPUS, google scholar and Cochrane identifying studies that reported on outcomes of surgical repair of ATAAD through either root preservation or replacement. The identified articles focused on short- and long-term mortalities, and rates of re-operation on the aortic root. Results: There remains controversy on replacing or preserving aortic root in ATAAD. Current evidence supports practice of both trends following an extensive decision-making framework, with conflicting series suggesting favourable results with both procedures as the approach that best defines higher survival rates and lower perioperative complications. Yet, the decision to perform either approach remains surgeon decision and bound to the extent of the dissection and tear entries in strong correlation with status of the aortic valve and involvement of coronaries in the dissection. Conclusions: There exists much controversy regarding fate of the aortic root in ATAAD. There are conflicting studies for impact of root replacement on mortality, whilst some study’s report no significant results at all. There is strong evidence regarding risk of re-operation being greater when root is not replaced. Majority of these studies are limited by the single centred, retrospective nature of these small sample sized cohorts, further hindered by potential of treatment bias.

Matthew Sussman

and 9 more

The recognition of fibrinolysis phenotypes in trauma patients has led to a reevaluation of antifibrinolytic therapy (AF). Many cardiac patients also receive AF, however the distribution of fibrinolytic phenotypes in that population is unknown. The purpose of this study was to fill that gap. Methods: Data were retrospectively reviewed from 78 cardiac surgery patients. Phenotypes were defined as hypofibrinolytic (LY30 <0.8%), physiologic (LY30 0.8-3.0%) and hyperfibrinolytic (LY30 >3%). Continuous variables were expressed as M ± SD or median (interquartile range). Results: The study population was 65±10 yrs old, 74% male, average body mass index of 29±5 kg/m2. Fibrinolytic phenotypes were distributed as physiologic=45%, hypo=32% and hyper = 23%. There was no obvious effect of age, gender, race, or ethnicity on the distribution of fibrinolysis phenotypes; 47% received AF. The time with chest tube during post-operative recovery was longer in those who received AF (4[3,5] days) vs no AF (3[2,4] days), P=0.037). All cause morbidity occurred in 51% of patients who received AF vs 25% with no AF (p=0.017). However, with AF vs no AF, apparent differences in median chest tube output (1379 vs 820ml, p=0.075), hospital LOS (13 vs 10 days, P=0.873), estimated blood loss (1100 vs 775 ml, P=0.127), units of transfused RBCs (4 vs 2], P=0.152) or all-cause mortality (5.4% [2/37] vs 10% [4/41], P=0.518) were not statistically significant. Conclusion: This is the first description of three distinctly different fibrinolytic phenotypes in cardiac surgery patients. In this population, the use of AF was associated with increased morbidity.

Arushi Singh

and 6 more

Background: Ibrutinib is associated with atrial fibrillation (AF), though echocardiographic predictors of AF have not been studied in this population. We sought to determine whether left atrial (LA) strain on transthoracic echocardiography could identify patients at risk for developing ibrutinib-related atrial fibrillation (IRAF). Methods: We performed a retrospective review of 66 patients who had an echocardiogram prior to ibrutinib treatment. LA strain was measured with TOMTEC Imaging Systems, obtaining peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) on 4-chamber and 2-chamber views. Statistical analysis was performed with Chi-square analysis, T-test, or binomial regression analysis, with a p-value < 0.05 considered statistically significant. Results: Twenty-two patients developed IRAF (33%). Age at initiation of ibrutinib was significantly associated with IRAF (65.1 years vs. 74.1 years, p = 0.002). Mean ibrutinib dose was lower among patients who developed IRAF (388.2 ± 121.7 vs. 448.6 ± 88.4, p = 0.025). E/e’ was significantly higher among patients who developed IRAF (11.5 vs. 9.3, p = 0.04). PALS was significantly lower in patients who developed AF (30.3% vs. 36.3%, p = 0.01). On multivariate regression analysis, age, PALS and PACS were significantly associated with IRAF. On multivariate regression analysis, only PACS remained significantly associated with IRAF while accounting for age. Conclusions: Age, ibrutinib dose, E/e’, and PALS on pre-treatment echocardiogram were significantly associated with development of IRAF. On multivariate regression analyses, age, PALS and PACS remained significantly associated with IRAF. Impaired LA mechanics add to the assessment of patients at risk for IRAF

James Hummel

and 1 more

We thank Medina et al. for their interest in our recent work on QTc prolongation associated with treatment of COVID-19 patients with hydroxychloroquine and azithromycin. As they appropriately point out in their letter, genetic variation is likely a significant determinant of QT prolongation in the population at large and in COVID-19 patients specifically. While drugs causing acquired long QT syndrome and torsades de pointes are generally blockers of IKr, repolarization results from the aggregate of multiple inward and outward currents. Patients with sub-clinical defects in any of these ion channels can have normal or only slightly prolonged baseline QT intervals, but may possess decreased repolarization reserve leading to an exaggerated response to IKr blockade (1).  In our study, a baseline QTc of > 460 ms was associated with excessive QTc prolongation, and this likely represents a group of patients with sub-clinical cardiac ion channel mutations (so called “first hit”) (2). We also agree that many patients with latent mutations demonstrate a normal baseline QT, which gets prolonged with the addition of a drug or a change in the clinical condition “second hit” (3). The patients in our study who exhibited QTc prolongation were generally acutely ill, and displayed “multiple hits” that led to QTc prolongation and it is certainly plausible that many may have had sub-clinical cardiac ion mutations. We therefore wholeheartedly agree that pharmacogenetics should be considered in studies of drug-induced QT prolongation, however this information is rarely available to include for acutely ill patients. And while it makes sense to obtain genetic profiles prior to administration of QT-prolonging medications, that can only be performed in the elective outpatient setting, while taking into consideration medical, ethical and social issues related to asymptomatic genetic screening (e.g. cost, reimbursement, informed consent, etc…). There is significant interest in building genomic databases, and when this becomes a reality for the population at large we believe that genetic information should certainly be included in studies of QT prolongation.Roden DM Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. 2006 Jan; 259(1):59-69.Napolitano C, Schwartz PJ, Brown AM, et al. Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias. J Cardiovasc Electrophysiol. 2000;11:691–6Sauer AJ and Newton-Cheh C. Clinical and genetic determinants of torsade de pointes risk. Circulation. 2012;125:1684-94.

Norman Mukarati

and 10 more

Numerous unknown factors influence anthrax epidemiology in multi-host systems, especially at wildlife/livestock/human interfaces. Serology tests for anti-anthrax antibodies in carnivores are useful tools in identifying the presence or absence of Bacillus anthracis in a range. These were employed to ascertain if the disease pattern followed the recognized high and low risk anthrax zonation in Zimbabwe and also to establish if anthrax was absent from Hwange National Park in which there has been no reported outbreaks. African lions (Panthera leo) (n= 114) drawn from -free-range protected areas and captive game parks located in recognized high and low risk zones across Zimbabwe were tested for antibodies to anthrax PA antigen using the ELISA immunoassay. A random selection of 27 lion sera samples comprising 17 sero-positive and 10 sero-negative sera were further tested in the species-independent toxin neutralization assay (TNA) in order to validate the former as a surveillance tool for anthrax in African lions. Using the ELISA-PA immunoassay, 21.9% (25/114) of the lions tested positive for antibodies to anthrax. Seropositivity was recorded in all study areas and there was no significant difference (p= 0.852) in seropositivity between lions in high and low risk anthrax zones. Also, there was no significant difference (McNemar’s χ2 = 0.9, p = 0.343) in the proportion of lions testing positive to anti-PA anthrax antibodies on ELISA-PA immunoassay compared to the TNA, with fair agreement between the two tests [Kappa (K) statistic = 0.30; 0.08

Roberto CHIESA

and 3 more

During the first phase of COVID-19 pandemic in Italy, several strategies have been taken to deal with the pandemic outbreak. The Regional Authority of Lombardy remodeled the hospitalization system in order to allocate appropriate resources to treat COVID-19 patients and to identify “Hub/Spoke” hospitals for highly specialized medical activities. The Hubs hospitals were required to guarantee full time evaluation of all patients presenting with cardiovavascular diseases with an independent pathway for patients with suspect or confirmed COVID-19 infection. San Raffaele Hospital was identified as Hub for cardiovascular emergencies and the Vascular Surgery Department was remodeled to face this epidemic situation. Surgical treatment was reserved only to symptomatic, urgent or emergent cases. Large areas of the hospital were simultaneously reorganized to assist COVID-19 patients. During this period, 135 patients were referred to San Raffaele Vascular Surgery Department. COVID-19 was diagnosed in 24 patients and, among them, acute limb ischemia was the most common cause of admission. At this time, the COVID-19 trend is in decline in Italy and the local authorities reorganized the health care system in order to return to normal activities avoiding new escalations of COVID-19 cases. Several strategies have been taken to ensure the safety of the San Raffaele hospital, and maintaining potentially suspected patients with COVID-19 separated from other patients. The aim of this paper is to report the remodeling of the Vascular Surgery Department of San Raffaele Hospital as regards the strategies of preparation, escalation, de-escalation and return to normal activities during the COVID-19 pandemic.

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