Efficacy and Safety of Activated Prothrombin Complex Concentrate for Reversal of the Anticoagulant Effect of Apixaban and Rivaroxaban in Patients with Major Bleeding.

BACKGROUND: The use of activated prothrombin complex concentrate (aPCC) to treat direct oral anticoagulant (DOAC)-associated bleeding is off-label and clinical experience is limited. OBJECTIVES: We aimed to assess the efficacy and safety of aPCC in reversing the anticoagulant effect of apixaban and rivaroxaban in patients presenting with major bleeding. METHODS: A retrospective cohort study of adult non-randomized patients was conducted at a tertiary referral medical center in the United States (US) to investigate the use of aPCC for the reversal of the anticoagulant effect of apixaban and rivaroxaban in patients presenting with major bleeding. The primary outcome was achieving clinical hemostasis according to prespecified criteria. Safety outcomes included the occurrence of thrombotic events during hospitalization. RESULTS: A total of 217 patients were included in the study. Intracranial hemorrhage (ICH) was the most common site of bleeding (n = 100, 46.1%), followed by gastrointestinal bleed (n = 87, 40.1%). Clinical hemostasis was achieved in 170 patients (78.3%), and the risk of not achieving hemostasis with ICH-related bleeding was significantly higher than that of non-ICH-related bleeding (2.5, 95% confidence interval [CI] 1.44-4.34; p < 0.001). Eight patients not achieving hemostasis died during hospitalization, all of whom were suffering from ICH, and mortality associated with non-ICH-related bleeding was significantly lower compared with ICH-related bleeding (0.91, 95% CI 0.86-0.97; p < 0.001). Thromboembolic events during hospitalization occurred in one patient (0.5%). CONCLUSIONS: The use of aPCC for the management of apixaban- or rivaroxaban-related major bleeding is effective in most cases and is associated with a low risk of thromboembolism.

Composition and assembly mechanisms of prokaryotic communities in wetlands, and their relationships with different vegetation and reclamation methods.

Coastal wetlands are undergoing substantial transformations globally as a result of increased human activities. However, compared to other ecosystems, diversity and functional characteristics of microbial communities in reclaimed coastal wetlands are not well studied compared to other ecosystems. This is important because it is known that microorganisms can play a crucial role in biogeochemical cycling within coastal wetland ecosystems. Hence, this study utilized the high-throughput sequencing technique to investigate the structure and assembly processes of microbial communities in reclaimed coastal wetlands. The results revealed a substantial change in soil properties following coastal wetland reclamation. Remarkably, the reclaimed soil exhibited significantly lower pH, soil organic carbon (SOC), and total salinity (TS) values (p < 0.05). The dominant phyla included Proteobacteria, Chloroflexi, Bacteroidetes, Acidobacteria, and Planctomycetes among study sites. However, the relative abundance of Proteobacteria increased from un-reclaimed coastal wetlands to reclaimed ones. The Proteobacteria, Chloroflexi, and Acidobacteria showed higher relative abundance in vegetated soil compared to bare soil, while Bacteroidetes and Planctomycetes exhibited the opposite trend. Notably, vegetation types exerted the strongest influence on microbial diversity, surpassing the effects of soil types and depth (F = 34.49, p < 0.001; F = 25.49, p < 0.001; F = 3.173, p < 0.078, respectively). Stochastic assembly processes dominated in un-reclaimed soil, whereas deterministic processes governed the assembly in artificial sea embankment wetlands (SEW). The presence of Spartina alterniflora in all soil types (except SEW soils) indicated stochastic assembly, while Phragmites australis in reclaimed soils pointed toward deterministic microbial assembly. Furthermore, environmental factors such as pH, soil water content (SWC), SOC, total carbon (TC), total nitrogen (TN), total phosphorus (TP), NH4+-N, vegetation types, soil depth, and geographic distance exhibited significant effects on microbial beta diversity indices. Co-occurrence network analysis revealed a stronger association between taxa in SEW compared to land reclaimed from wetlands (LRW) and natural coastal wetlands (NCW). The bottom soil layer exhibited more complex network interactions than the topsoil layer. Besides soil parameters, reclamation and varieties of vegetation were also substantial factors influencing the composition, diversity, and assembly processes of microbial communities in coastal wetlands.

Volatile Organic Compounds Emitted by the Biocontrol Agent Pythium oligandrum Contribute to Ginger Plant Growth and Disease Resistance.

The oomycete Pythium oligandrum is a potential biocontrol agent to control a wide range of fungal and oomycete-caused diseases, such as Pythium myriotylum-caused rhizome rot in ginger, leading to reduced yields and compromised quality. Previously, P. oligandrum has been studied for its plant growth-promoting potential by auxin production and induction of disease resistance by elicitors such as oligandrin. Volatile organic compounds (VOCs) play beneficial roles in sustainable agriculture by enhancing plant growth and resistance. We investigated the contribution of P. oligandrum-produced VOCs on plant growth and disease suppression by initially using Nicotiana benthamiana plants for screening. P. oligandrum VOCs significantly enhanced tobacco seedling and plant biomass contents. Screening of the individual VOCs showed that 3-octanone and hexadecane promoted the growth of tobacco seedlings. The total VOCs from P. oligandrum also enhanced the shoot and root growth of ginger plants. Transcriptomic analysis showed a higher expression of genes related to plant growth hormones and stress responses in the leaves of ginger plants exposed to P. oligandrum VOCs. The concentrations of plant growth hormones such as auxin, zeatin, and gibberellic acid were higher in the leaves of ginger plants exposed to P. oligandrum VOCs. In a ginger disease biocontrol assay, the VOC-exposed ginger plants infected with P. myriotylum had lower levels of disease severity. We conclude that this study contributes to understanding the growth-promoting mechanisms of P. oligandrum on ginger and tobacco, priming of ginger plants against various stresses, and the mechanisms of action of P. oligandrum as a biocontrol agent. IMPORTANCE Plant growth promotion plays a vital role in enhancing production of agricultural crops, and Pythium oligandrum is known for its plant growth-promoting potential through production of auxins and induction of resistance by elicitors. This study highlights the significance of P. oligandrum-produced VOCs in plant growth promotion and disease resistance. Transcriptomic analyses of leaves of ginger plants exposed to P. oligandrum VOCs revealed the upregulation of genes involved in plant growth hormone signaling and stress responses. Moreover, the concentration of growth hormones significantly increased in P. oligandrum VOC-exposed ginger plants. Additionally, the disease severity was reduced in P. myriotylum-infected ginger plants exposed to P. oligandrum VOCs. In ginger, P. myriotylum-caused rhizome rot disease results in severe losses, and biocontrol has a role as part of an integrated pest management strategy for rhizome rot disease. Overall, growth enhancement and disease reduction in plants exposed to P. oligandrum-produced VOCs contribute to its role as a biocontrol agent.

Plant-Microbes Interaction: Exploring the Impact of Cold-Tolerant Bacillus Strains RJGP41 and GBAC46 Volatiles on Tomato Growth Promotion through Different Mechanisms.

The interaction between plant and bacterial VOCs has been extensively studied, but the role of VOCs in growth promotion still needs to be explored. In the current study, we aim to explore the growth promotion mechanisms of cold-tolerant Bacillus strains GBAC46 and RJGP41 and the well-known PGPR strain FZB42 and their VOCs on tomato plants. The result showed that the activity of phytohormone (IAA) production was greatly improved in GBAC46 and RJGP41 as compared to FZB42 strains. The in vitro and in-pot experiment results showed that the Bacillus VOCs improved plant growth traits in terms of physiological parameters as compared to the CK. The VOCs identified through gas chromatography-mass spectrometry (GC-MS) analysis, namely 2 pentanone, 3-ethyl (2P3E) from GBAC46, 1,3-cyclobutanediol,2,2,4,4-tetramethyl (CBDO) from RJGP41, and benzaldehyde (BDH) from FZB42, were used for plant growth promotion. The results of the partition plate (I-plate) and in-pot experiments showed that all the selected VOCs (2P3E, CBDO, and BDH) promoted plant growth parameters as compared to CK. Furthermore, the root morphological factors also revealed that the selected VOCs improved the root physiological traits in tomato plants. The plant defense enzymes (POD, APX, SOD, and CAT) and total protein contents were studied, and the results showed that the antioxidant enzymes and protein contents significantly increased as compared to CK. Similarly, plant growth promotion expression genes (IAA4, ARF10A, GA2OX2, CKX2, and EXP1) were significantly upregulated and the ERF gene was downregulated as compared to CK. The overall findings suggest that both Bacillus isolates and their pure VOCs positively improved plant growth promotion activities by triggering the antioxidant enzyme activity, protein contents, and relative gene expressions in tomato plants.

Volatile Organic Compounds from Pythium oligandrum Play a Role in Its Parasitism on Plant-Pathogenic Pythium myriotylum.

The oomycete Pythium oligandrum is a soil-inhabiting parasite and predator of both fungi and oomycetes, and uses hydrolytic enzymes extensively to penetrate and hydrolyze its host or prey. Other mechanisms have been studied less, and we investigated the contribution of P. oligandrum-produced volatile organic compounds (VOCs) to parasitism. The growth-inhibiting activity of P. oligandrum VOCs was tested on Pythium myriotylum-a host or prey of P. oligandrum-coupled with electron microscopy, and biochemical and transcriptomic analyses. The P. oligandrum-produced VOCs reduced P. myriotylum growth by 80% and zoospore levels by 60%. Gas chromatography-mass spectrometry (GC-MS) identified 23 VOCs, and methyl heptenone, d-limonene, 2-undecanone, and 1-octanal were potent inhibitors of P. myriotylum growth and led to increased production of reactive oxygen species at a concentration that did not inhibit P. oligandrum growth. Exposure to the P. oligandrum VOCs led to shrinkage of P. myriotylum hyphae and lysis of the cellular membranes and organelles. Transcriptomics of P. myriotylum exposed to the P. oligandrum VOCs at increasing levels of growth inhibition initially showed a strong upregulation of putative detoxification-related genes that was not maintained later. The inhibition of P. myriotylum growth continued immediately after the exposure to the VOCs was discontinued and led to the reduced infection of its plant hosts. The VOCs produced by P. oligandrum could be another factor alongside hydrolytic enzymes contributing to its ecological role as a microbial parasite in particular ecological niches such as in soil, and may also contribute to the biocontrol of diseases using P. oligandrum commercial preparations. IMPORTANCE Microbe-microbe interactions in nature are multifaceted, with multiple mechanisms of action, and are crucial to how plants interact with microbes. Volatile organic compounds (VOCs) have diverse functions, including contributing to parasitism in ecological interactions and potential applications in biocontrol. The microbial parasite P. oligandrum is well known for using hydrolytic enzymes as part of its parasitism. We found that P. oligandrum VOCs reduced the growth of, and caused major damage to, the hyphae of P. myriotylum (a host or prey of P. oligandrum). Transcriptomic analyses of P. myriotylum exposed to the VOCs revealed the upregulation of genes potentially involved in an attempt to detoxify the VOCs. The inhibitory effects of the VOCs had a knock-on effect by reducing the virulence of P. myriotylum toward its plant hosts. The P. oligandrum VOCs could contribute to its ecological role as a microbial parasite. The VOCs analyzed here may also contribute to the biocontrol of diseases using P. oligandrum commercial preparations.

Risk Factors Associated With Six-Month Mortality in Hospitalized COVID-19 Patients: A Single-Institution Study.

Background Coronavirus disease 2019 (COVID-19) infection can vary from asymptomatic infection to multi-organ dysfunction. The most serious complication of infection with COVID-19 is death. Various comorbid conditions and inflammatory markers have been associated with an increased risk of mortality, specifically within the immediate post-infection period; however, less is known about long-term mortality outcomes. Objectives Our objective is to determine risk factors associated with six-month mortality in hospitalized COVID-19 patients. Methods This is a single-institution, retrospective study. We included patients hospitalized with COVID-19 from the University of Toledo Medical Center in Toledo, Ohio, who were admitted from March 20, 2020, to June 30, 2021. This study was approved by a biomedical institutional review board at the University of Toledo. Patients with available pre-stored blood samples for laboratory testing were included, and hospital charts were assessed up to six months from the date of a positive COVID-19 test result. Two groups were created based on the mortality outcome at six months from COVID-19 positive test results: survivors and non-survivors. The clinical variables or outcomes and laboratory values were compared between the two groups using non-parametric methods due to the small sample size and non-normality of the data. Either the Mann-Whitney U-test for continuous variables or Fisher's exact test for categorical variables was used for statistical analysis. Results Lactate dehydrogenase (LDH) and D-dimer levels on admission were found to be significantly higher in non-survivors than in survivors. The median high D-dimer level in non-survivors was 5.96 micrograms/milliliter (µg/mL) (interquartile range (IQR): 3.95-11.29 µg/mL) vs 1.82 µg/mL (IQR 1.13-5.55 µg/mL) in survivors (p = 0.019). Median LDH levels were also higher in non-survivors vs survivors, i.e., 621.00 international units per liter (IU/L) (IQR 440.00-849.00 IU/L) vs 328.00 IU/L (IQR 274.00-529.00 IU/L), respectively (p = 0.032). The demographic profile, comorbidity profile, and laboratory data (typically associated with short-term mortality, inflammation, and organ dysfunction) were similar between survivors and non-survivors, except for LDH and D-dimer. Conclusion Higher LDH and D-dimer levels on admission were found to be associated with an increased six-month mortality rate in hospitalized COVID-19 patients. These hematologic data can serve as risk stratification tools to prevent long-term mortality outcomes and provide proactive clinical care in hospitalized COVID-19 patients.

Melanoma Treatments and Mortality Rate Trends in the US, 1975 to 2019.

Importance: Melanoma accounts for most of the deaths due to skin cancer. In the past decade, effective US Food and Drug Administration (FDA)-approved therapies for melanoma have emerged. Objective: To review changes in the long-term melanoma mortality rate (MMR) trends in the US and determine whether they have any temporal association with the FDA approval of new agents. Design, Setting, and Participants: This cross-sectional study used population data from the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed the age-adjusted MMR trends in adult patients (aged ≥18 years) from 1975 to 2019 in the US population. The timeline of the FDA approvals for melanoma treatment was also reviewed. Data were analyzed from March 15 to August 15, 2022. Exposures: Outcomes were assessed in association with FDA approval of drugs for the treatment of melanoma. Main Outcomes and Measures: Mortality rates are from the SEER database, reported per 100 000 population and age-adjusted to the 2000 US standard population. The annual percent change (APC) has been used to report long-term trends. Results: After the introduction of newer treatments in 2011 (most after 2013), a significant reduction in MMR was seen from 2013 to 2017 in the US for the first time in the past 40 years. Rates increased from 1975 to 1988 (APC, 1.65% [95% CI, 1.30%-2.00%]; P < .001). No statistically significant change in MMR was seen from 1988 to 2013 (APC, 0.01% [95% CI, -1.10% to 0.12%]; P = .85). The MMR decreased significantly from 2013 to 2017 (APC, -6.28% [95% CI, -8.52% to -3.97%]; P < .001). Conclusions and Relevance: These findings suggest a benefit associated with the availability of effective therapies in the past decade and further suggest that the use of new pharmacological therapies is associated with decreased MMR in the US population. These data are very encouraging and support the continued development of such therapies. Additionally, the accessibility of these treatments and the associated health care costs need to be addressed.

Copper deficiency, a rare but correctable cause of pancytopenia: a review of literature.

INTRODUCTION: Copper is increasingly being recognized as a vital mineral required by both animals and humans. It plays a vital role in many metabolic processes such as cellular respiration, iron oxidation, and hemoglobin synthesis. Copper deficiency, which can be hereditary or acquired, can lead to a wide spectrum of disease processes such as ringed sideroblastic anemia, myelodysplasia, and pancytopenia. Timely identification and management of copper deficiency is necessary to prevent irreversible complications. AREAS COVERED: Our study focuses on prevalence, etiology, pathophysiology, complications, and treatment of copper deficiency. EXPERT OPINION: Copper deficiency is frequently underrecognized as the cause of anemia, neutropenia, and bone marrow dysplasia. As it is potentially treatable, it should always be kept in the differentials when patients present with neurological and hematological abnormalities.

Prevalence and Clinical Significance of Antiphospholipid Antibodies in Hospitalized Patients With COVID-19 Infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of arterial thromboembolic events (ATE) and venous thromboembolic events (VTE). Hypercoagulability associated with COVID-19 infection is multifactorial, and underlying pathogenic mechanisms potentially responsible for thrombosis include inflammation resulting in endothelial damage, platelet activation and the presence of antiphospholipid antibodies (APAs). Antiphospholipid antibody syndrome is one of the very few causes which is associated with venous and arterial thromboembolic events. COVID-19 patients have a high prevalence of APAs as well as both ATE and VTE, but their clinical significance in COVID-19 patients is not fully understood yet. OBJECTIVES: In this study, we intend to find the prevalence of APAs in hospitalized COVID-19 patients at the time of diagnosis and determine whether their presence has any clinical significance. METHODS: This is a retrospective single-institution study involving patients hospitalized for the management of COVID-19 infection at The University of Toledo Medical Center. After obtaining approval from the biomedical institutional review board at The University of Toledo, antiphospholipid antibody (APA) testing was done on pre-stored blood samples of these patients and hospital charts were reviewed till six months from the positive COVID-19 test result. Two groups were created based on the patients' APA testing results (APA positive and APA negative) and used for statistical comparison. Any patients with positive lupus anticoagulant (LA) or abnormal titers APA antibodies were labeled as positive. Demographic data, prognostic outcomes and laboratory values were compared either using Mann-Whitney U-test for continuous variables or Fisher's exact test for categorical variables. RESULTS: The prevalence of APAs in hospitalized COVID-19 patients at the time of diagnosis was 39.3% in this study. There was no difference in demographic variables between the APA-positive and APA-negative groups. The prevalence of APAs was higher in smokers, where 91% of the APA-positive patients were smokers. There was no statistically significant difference in prognostic outcomes including six-month mortality between APA-positive and APA-negative patients. The comorbidity profile was the same in the two groups. APA-positive patients were found to have lower nadir of absolute lymphocyte count and higher nadir levels of C-reactive protein during hospitalization. CONCLUSIONS: The prevalence of APA positivity in hospitalized COVID-19 patients is higher in our study than in historical studies involving non-COVID-19 hospitalized patients, particularly in smokers. However, there is no correlation between APA positivity and prognostic outcomes including six-month mortality. At this point, it is unclear whether APAs are just bystanders or have a pathogenic role. Routine testing of APA in COVID-19 patients is not indicated. Further prospective studies to elucidate the persistence and clinical implications of APAs are needed.

Genome of Pythium myriotylum Uncovers an Extensive Arsenal of Virulence-Related Genes among the Broad-Host-Range Necrotrophic Pythium Plant Pathogens.

The Pythium (Peronosporales, Oomycota) genus includes devastating plant pathogens that cause widespread diseases and severe crop losses. Here, we have uncovered a far greater arsenal of virulence factor-related genes in the necrotrophic Pythium myriotylum than in other Pythium plant pathogens. The genome of a plant-virulent P. myriotylum strain (~70 Mb and 19,878 genes) isolated from a diseased rhizome of ginger (Zingiber officinale) encodes the largest repertoire of putative effectors, proteases, and plant cell wall-degrading enzymes (PCWDEs) among the studied species. P. myriotylum has twice as many predicted secreted proteins than any other Pythium plant pathogen. Arrays of tandem duplications appear to be a key factor of the enrichment of the virulence factor-related genes in P. myriotylum. The transcriptomic analysis performed on two P. myriotylum isolates infecting ginger leaves showed that proteases were a major part of the upregulated genes along with PCWDEs, Nep1-like proteins (NLPs), and elicitin-like proteins. A subset of P. myriotylum NLPs were analyzed and found to have necrosis-inducing ability from agroinfiltration of tobacco (Nicotiana benthamiana) leaves. One of the heterologously produced infection-upregulated putative cutinases found in a tandem array showed esterase activity with preferences for longer-chain-length substrates and neutral to alkaline pH levels. Our results allow the development of science-based targets for the management of P. myriotylum-caused disease, as insights from the genome and transcriptome show that gene expansion of virulence factor-related genes play a bigger role in the plant parasitism of Pythium spp. than previously thought. IMPORTANCE Pythium species are oomycetes, an evolutionarily distinct group of filamentous fungus-like stramenopiles. The Pythium genus includes several pathogens of important crop species, e.g., the spice ginger. Analysis of our genome from the plant pathogen Pythium myriotylum uncovered a far larger arsenal of virulence factor-related genes than found in other Pythium plant pathogens, and these genes contribute to the infection of the plant host. The increase in the number of virulence factor-related genes appears to have occurred through the mechanism of tandem gene duplication events. Genes from particular virulence factor-related categories that were increased in number and switched on during infection of ginger leaves had their activities tested. These genes have toxic activities toward plant cells or activities to hydrolyze polymeric components of the plant. The research suggests targets to better manage diseases caused by P. myriotylum and prompts renewed attention to the genomics of Pythium plant pathogens.

Zinc Essentiality, Toxicity, and Its Bacterial Bioremediation: A Comprehensive Insight.

Zinc (Zn) is one of the most abundantly found heavy metals in the Earth's crust and is reported to be an essential trace metal required for the growth of living beings, with it being a cofactor of major proteins, and mediating the regulation of several immunomodulatory functions. However, its essentiality also runs parallel to its toxicity, which is induced through various anthropogenic sources, constant exposure to polluted sites, and other natural phenomena. The bioavailability of Zn is attributable to various vegetables, beef, and dairy products, which are a good source of Zn for safe consumption by humans. However, conditions of Zn toxicity can also occur through the overdosage of Zn supplements, which is increasing at an alarming rate attributing to lack of awareness. Though Zn toxicity in humans is a treatable and non-life-threatening condition, several symptoms cause distress to human activities and lifestyle, including fever, breathing difficulty, nausea, chest pain, and cough. In the environment, Zn is generally found in soil and water bodies, where it is introduced through the action of weathering, and release of industrial effluents, respectively. Excessive levels of Zn in these sources can alter soil and aquatic microbial diversity, and can thus affect the bioavailability and absorption of other metals as well. Several Gram-positive and -negative species, such as Bacillus sp., Staphylococcus sp., Streptococcus sp., and Escherichia coli, Pseudomonas sp., Klebsiella sp., and Enterobacter sp., respectively, have been reported to be promising agents of Zn bioremediation. This review intends to present an overview of Zn and its properties, uses, bioavailability, toxicity, as well as the major mechanisms involved in its bioremediation from polluted soil and wastewaters.

The Use of Opioids and Pain Medications in the Management of Postoperative Pain in Total Knee Arthroplasty Patients: A Retrospective Study.

Purpose: The opioid crisis amplified the concern for the appropriate use of opioids. Our study aims to investigate the pain levels and amount of opiates needed during the first three days following total knee arthroplasty (TKA), whereby Drug Enforcement Administration (DEA) Schedule II oral opiates are not available. Methods: A year-long retrospective review of adult patients who underwent TKA was conducted. The postoperative pain scores and mean morphine equivalents (MME) were measured. These outcomes were assessed according to demographics, anesthesia, and analgesia used. Results: For our 78 patients, there was no statistical difference for stratification by baseline characteristics except in spinal anesthesia, which decreased pain on the first day. Conversely, MME increased to its significantly highest of 14.22 ± 29.58 mg on day 3. The effect was noted for patient-controlled analgesia where patients with intravenous analgesia received less opioid than those on epidural analgesia on postoperative day one. Conclusions: Using a similar regimen of analgesia, postoperative pain following TKA would be controlled by a relatively low amount of opioids by the third postoperative day. Spinal anesthesia and patient-controlled epidural analgesia were linked to better pain control and less opioid needed.

Efficacy and safety of activated prothrombin complex concentrate for the reversal of vitamin K antagonist major bleeding.

Data on the use of activated prothrombin complex concentrate (aPCC) for the management of warfarin associated major bleeding is sparse. The objective of the study was to assess the achievement of effective clinical hemostasis using aPCC in patients presenting with major bleeding while on warfarin. We also assessed the safety of the drug. This retrospective study was conducted at a tertiary care teaching center in the USA where patients with major bleeding while receiving warfarin, and received aPCC were included. Efficacy of aPCC in achieving effective hemostasis was assessed according to the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria. Efficacy was also assessed by achieving INR < 1.5 after treatment. The primary safety endpoint was the occurrence of any thromboembolic complications. A total of 67 patients were included in the study. The most common site for bleeding was intracerebral hemorrhage (n = 37, 55.2%), followed by gastrointestinal bleed (n = 26, 38.8%). Clinical hemostasis was achieved in 46 (68.7%) patients and of the 21 (31.3%) patients who did not achieve clinical hemostasis, 16 died. Thirty nine (58.2%) patients achieved INR < 1.5. Five (7.5%) patients developed thromboembolic complications. This study suggests that the use of aPCCs is effective in achieving effective hemostasis in patients on warfarin presenting with major bleeding.

Corrigendum: Zinc essentiality, toxicity, and its bacterial bioremediation: A comprehensive insight.

[This corrects the article DOI: 10.3389/fmicb.2022.900740.].

Dual-Transcriptomic, Microscopic, and Biocontrol Analyses of the Interaction Between the Bioeffector Pythium oligandrum and the Pythium Soft-Rot of Ginger Pathogen Pythium myriotylum.

Biological control is a promising approach to suppress diseases caused by Pythium spp. such as Pythium soft rot of ginger caused by P. myriotylum. Unusually for a single genus, it also includes species that can antagonize Pythium plant pathogens, such as Pythium oligandrum. We investigated if a new isolate of P. oligandrum could antagonize P. myriotylum, what changes occurred in gene expression when P. oligandrum (antagonist) and P. myriotylum (host) interacted, and whether P. oligandrum could control soft-rot of ginger caused by P. myriotylum. An isolate of P. oligandrum, GAQ1, recovered from soil could antagonize P. myriotylum in a plate-based confrontation assay whereby P. myriotylum became non-viable. The loss of viability of P. myriotylum coupled with how P. oligandrum hyphae could coil around and penetrate the hyphae of P. myriotylum, indicated a predatory interaction. We investigated the transcriptional responses of P. myriotylum and P. oligandrum using dual-RNAseq at a stage in the confrontation where similar levels of total transcripts were measured from each species. As part of the transcriptional response of P. myriotylum to the presence of P. oligandrum, genes including a subset of putative Kazal-type protease inhibitors were strongly upregulated along with cellulases, elicitin-like proteins and genes involved in the repair of DNA double-strand breaks. In P. oligandrum, proteases, cellulases, and peroxidases featured prominently in the upregulated genes. The upregulation along with constitutive expression of P. oligandrum proteases appeared to be responded to by the upregulation of putative protease inhibitors from P. myriotylum, suggesting a P. myriotylum defensive strategy. Notwithstanding this P. myriotylum defensive strategy, P. oligandrum had a strong disease control effect on soft-rot of ginger caused by P. myriotylum. The newly isolated strain of P. oligandrum is a promising biocontrol agent for suppressing the soft-rot of ginger. The dual-RNAseq approach highlights responses of P. myriotylum that suggests features of a defensive strategy, and are perhaps another factor that may contribute to the variable success and durability of biological attempts to control diseases caused by Pythium spp.

Novel Genetic Dysregulations and Oxidative Damage in Fusarium graminearum Induced by Plant Defense Eliciting Psychrophilic Bacillus atrophaeus TS1.

This study elaborates inter-kingdom signaling mechanisms, presenting a sustainable and eco-friendly approach to combat biotic as well as abiotic stress in wheat. Fusarium graminearum is a devastating pathogen causing head and seedling blight in wheat, leading to huge yield and economic losses. Psychrophilic Bacillus atrophaeus strain TS1 was found as a potential biocontrol agent for suppression of F. graminearum under low temperature by carrying out extensive biochemical and molecular studies in comparison with a temperate biocontrol model strain Bacillus amyloliquefaciens FZB42 at 15 and 25 °C. TS1 was able to produce hydrolytic extracellular enzymes as well as antimicrobial lipopeptides, i.e., surfactin, bacillomycin, and fengycin, efficiently at low temperatures. The Bacillus strain-induced oxidative cellular damage, ultrastructural deformities, and novel genetic dysregulations in the fungal pathogen as the bacterial treatment at low temperature were able to downregulate the expression of newly predicted novel fungal genes potentially belonging to necrosis inducing protein families (fgHCE and fgNPP1). The wheat pot experiments conducted at 15 and 25 °C revealed the potential of TS1 to elicit sudden induction of plant defense, namely, H2O2 and callose enhanced activity of plant defense-related enzymes and induced over-expression of defense-related genes which accumulatively lead to the suppression of F. graminearum and decreased diseased leaf area.

First Reported Case of Deglutition Syncope With Underlying Suppurative Parotitis.

Deglutition syncope and carotid sinus hypersensitivity are neurally mediated events, leading to potentially dangerous arrhythmias and cardiovascular events. Mostly related to underlying gastroesophageal or cardiovascular causes, sometimes, this might not be the case. We report the first-ever documented case of deglutition syncope with acute suppurative parotitis, which resolved after resolving the parotid gland's swelling.

Epidemiological and Clinical Characteristics of 217 COVID-19 Patients in Northwest Ohio, United States.

Background There is limited data on the clinical characteristics and predictors of mortality of coronavirus disease-2019 (COVID-19) in North West Ohio. We performed a retrospective review of patients hospitalized with COVID-19 in the ProMedica Health System in Northwest Ohio from March 25 to June 16, 2020. The study aims to identify epidemiological, clinical characteristics, and predictors of Mortality of COVID-19 patients in Northwest Ohio. Methods This study was conducted on 217 COVID-19 patients admitted to ProMedica Health System Hospitals in Northwest Ohio from March 25 to June 16, 2020. We collected data, including clinical signs, symptoms, and outcomes of the COVID-19 patients. We compared clinical signs and symptoms along with comorbidities of survivors and non-survivors. Results Of the 217 patients included in the study, the mean age of the population was 63.13 (SD 17.8), of which 194 (89.4%, mean age 61.7 years) survived while 23 (10.6%, mean age 74.6 years) died. Among them, 53% were females and 47% male. Common presenting symptoms were chest pain (91.71%), shortness of breath (79.7%), cough (71%), and fever (64%). Mortality was associated with age greater than 63 (p-value 0.0052) and hypertension (p-value: 0.0058) with marginal significance with gender (p-value: 0.0642), chest pain (p-value: 0.0944), and history of cancer (p-value: 0.0944). Conclusions Advanced age and hypertension (HTN) are independent predictors for increased mortality. History of cancer and chest pain are associated with increased mortality with marginal significance. Awareness among physicians about predictors of mortality is essential in dealing with COVID-19 patients. It is essential to educate the public about preventative strategies such as wearing masks to decrease mortality and morbidity from this pandemic.

Gastric amyloidosis in a patient with dysphagia.

Dysphagia is a symptom with a broad differential diagnosis. Usually, the etiology of dysphagia is benign, but it is essential to rule out serious causes. It is also critical to think outside the box when the etiology is not obvious. Herein, we describe a case of multiple myeloma that initially presented with dysphagia. An 81-year-old male patient presented with dysphagia to solid food associated with anorexia and weight loss of 22 kg over the last 6 months. The patient looked chronically ill and cachectic. Upper endoscopy showed patchy erythema in the gastric antrum. Gastric biopsy was consistent with gastric amyloidosis. Although serum and urine protein electrophoresis did not show a monoclonal (M) band, immunofixation did show elevated free kappa light chains and elevated free Kappa/Lambda ratio. Bone marrow biopsy was consistent with multiple myeloma. Although gastrointestinal involvement is common in amyloidosis, it is unusual for amyloidosis to initially present in the gastrointestinal tract. Identification and treatment of the underlying condition, e.g., multiple myeloma, can lead to regression of gastrointestinal amyloidosis.