Women's reproductive health in the aftermath of natural disasters in Bangladesh: Prospects for empowerment.

In this study, the authors examine the effect of Cyclone Sidr in 2007 on selected aspects of women's reproductive decision-making in Bangladesh. We used Person in Environment theories to model the effect of cyclone Sidr on the reasons for non-contraception among women who did not want a child. The difference-in-difference approach was used as a research design using Bangladesh Demographic and Health Surveys of 2004 and 2011 to test a model of reasons for non-contraception among a subsample of women who did not want a child. Our results indicated that women experienced fewer social controls on contraceptive use decision-making in the aftermath of a natural disaster.

Vertical transmission and prevalence of white spot syndrome virus (WSSV) in the wild spawning population of the Indian white shrimp, Penaeus indicus.

White spot disease, caused by white spot syndrome virus (WSSV), has historically been the most devastating disease in shrimp aquaculture industry across the world. The mode of virus transmission is the most crucial stage in the dynamics and management of virus infection. This study explored the mechanism of vertical transmission of WSSV in Indian white shrimp, Penaeus indicus, potential native species for domestication and genetic improvement, using quantitative real time PCR (q RT PCR), light and electron microscopy, and in situ hybridization. Wild brooders of P. indicus (n = 2576) were sampled along the South east coast of India, during 2016 to 2021. Of these âˆ¼ 58 % of the brooders were positive for WSSV, and almost 50 % of infected wild brooders were at the various stages of reproductive maturation. WSSV-PCR positive brooders (n = 200) were analysed for vertical WSSV transmission. The q RT PCR studies of reproductive tissues revealed that 61 % (n = 13) of spermatophore, 54 % (n = 28) of immature ovaries and 48 % (n = 27) of ripe ovaries were infected with WSSV. The lowest level of infection was recorded in females with ripe ovaries (6.84 × 101 ± 9.79 × 100 ng genomic DNA) followed by fertilized eggs (1.59 × 102 ± 3.69 × 101 ng genomic DNA), and larvae (nauplius and zoea). The histology of gravid females with high WSSV copies showed pyknotic and karyorrhectic germinal vesicle with degenerated cortical rods. Conversely, the gravid females with low WSSV copies showed fully developed ovary without characteristic signs of WSSV infection. Transmission electron microscopic studies clearly established the presence of WSSV particles in both ovaries and spermatophores. When subjected to in situ hybridization, WSSV-specific signals were observed in connective tissues of spermatophore, although gravid ovary and fertilized eggs were failed to produce WSSV specific signals. The present study provides the first molecular and histological evidence for trans-ovarian vertical transmission of WSSV. Development of disease-free base population being the cornerstone and first step in establishing the breeding program, the present findings could be a basis for development of such programs.

Opposing Roles for the α Isoform of the Catalytic Subunit of Protein Phosphatase 1 in Inside-Out and Outside-In Integrin Signaling in Murine Platelets.

Platelet activation during hemostasis and thrombosis is facilitated by agonist-induced inside-out and integrin αIIbß3-initiated outside-in signaling via protein kinases and phosphatases. Pharmacological inhibitor studies suggest that the serine/threonine protein phosphatase 1 (PP1) promotes platelet activation. However, since phosphatase inhibitors block all the isoforms of the catalytic subunit of PP1 (PP1c), the role of specific PP1c isoform in platelet signaling remains unclear. Here, we employed a platelet-specific PP1cα-/- mice to explore the contribution of a major PP1 isoform in platelet functions. Loss of PP1cα moderately decreased activation of integrin αIIbß3, binding of soluble fibrinogen, and aggregation to low-dose thrombin, ADP, and collagen. In contrast, PP1cα-/- platelets displayed increased adhesion to immobilized fibrinogen, fibrin clot retraction, and thrombus formation on immobilized collagen. Mechanistically, post-fibrinogen engagement potentiated p38 mitogen-activated protein kinase (MAPK) activation in PP1cα-/- platelets and the p38 inhibitor blocked the increased integrin-mediated outside-in signaling function. Tail bleeding time and light-dye injury-induced microvascular thrombosis in the cremaster venules and arterioles were not altered in PP1cα-/- mice. Thus, PP1cα displays pleiotropic signaling in platelets as it amplifies agonist-induced signaling and attenuates integrin-mediated signaling with no impact on hemostasis and thrombosis.

Pediatric Swine Model of Methicillin-Resistant Staphylococcus aureus Sepsis-Induced Coagulopathy, Disseminated Microvascular Thrombosis, and Organ Injuries.

Sepsis-induced coagulopathy leading to disseminated microvascular thrombosis is associated with high mortality and has no existing therapy. Despite the high prevalence of Gram-positive bacterial sepsis, especially methicillin-resistant Staphylococcus aureus (MRSA), there is a paucity of published Gram-positive pediatric sepsis models. Large animal models replicating sepsis-induced coagulopathy are needed to test new therapeutics before human clinical trials. HYPOTHESIS: Our objective is to develop a pediatric sepsis-induced coagulopathy swine model that last 70 hours. METHODS AND MODELS: Ten 3 weeks old piglets, implanted with telemetry devices for continuous hemodynamic monitoring, were IV injected with MRSA (n = 6) (USA300, Texas Children's Hospital 1516 strain) at 1 × 109 colony forming units/kg or saline (n = 4). Fluid resuscitation was given for heart rate greater than 50% or mean arterial blood pressure less than 30% from baseline. Acetaminophen and dextrose were provided as indicated. Point-of-care complete blood count, prothrombin time (PT), activated thromboplastin time, d-dimer, fibrinogen, and specialized coagulation assays were performed at pre- and post-injection, at 0, 24, 48, 60, and 70 hours. Piglets were euthanized and necropsies performed. RESULTS: Compared with the saline treated piglets (control), the septic piglets within 24 hours had significantly lower neurologic and respiratory scores. Over time, PT, d-dimer, and fibrinogen increased, while platelet counts and activities of factors V, VII, protein C, antithrombin, and a disintegrin and metalloproteinase with thrombospondin-1 motifs (13th member of the family) (ADAMTS-13) decreased significantly in septic piglets compared with control. Histopathologic examination showed minor focal organ injuries including microvascular thrombi and necrosis in the kidney and liver of septic piglets. INTERPRETATIONS AND CONCLUSIONS: We established a 70-hour swine model of MRSA sepsis-induced coagulopathy with signs of consumptive coagulopathy, disseminated microvascular thrombosis, and early organ injuries with histological minor focal organ injuries. This model is clinically relevant to pediatric sepsis and can be used to study dysregulated host immune response and coagulopathy to infection, identify potential early biomarkers, and to test new therapeutics.

MRF: a tool to overcome the barrier of inconsistent genome annotations and perform comparative genomics studies for the largest animal DNA virus.

BACKGROUND: The genome of the largest known animal virus, the white spot syndrome virus (WSSV) responsible for huge economic losses and loss of employment in aquaculture, suffers from inconsistent annotation nomenclature. Novel genome sequence, circular genome and variable genome length led to nomenclature inconsistencies. Since vast knowledge has already accumulated in the past two decades with inconsistent nomenclature, the insights gained on a genome could not be easily extendable to other genomes. Therefore, the present study aims to perform comparative genomics studies in WSSV on uniform nomenclature. METHODS: We have combined the standard mummer tool with custom scripts to develop missing regions finder (MRF) that documents the missing genome regions and coding sequences in virus genomes in comparison to a reference genome and in its annotation nomenclature. The procedure was implemented as web tool and in command-line interface. Using MRF, we have documented the missing coding sequences in WSSV and explored their role in virulence through application of phylogenomics, machine learning models and homologous genes. RESULTS: We have tabulated and depicted the missing genome regions, missing coding sequences and deletion hotspots in WSSV on a common annotation nomenclature and attempted to link them to virus virulence. It was observed that the ubiquitination, transcription regulation and nucleotide metabolism might be essentially required for WSSV pathogenesis; and the structural proteins, VP19, VP26 and VP28 are essential for virus assembly. Few minor structural proteins in WSSV would act as envelope glycoproteins. We have also demonstrated the advantage of MRF in providing detailed graphic/tabular output in less time and also in handling of low-complexity, repeat-rich and highly similar regions of the genomes using other virus cases. CONCLUSIONS: Pathogenic virus research benefits from tools that could directly indicate the missing genomic regions and coding sequences between isolates/strains. In virus research, the analyses performed in this study provides an advancement to find the differences between genomes and to quickly identify the important coding sequences/genomes that require early attention from researchers. To conclude, the approach implemented in MRF complements similarity-based tools in comparative genomics involving large, highly-similar, length-varying and/or inconsistently annotated viral genomes.

Transgender theory revisited: Current applications to transgender issues.

In addition to social determinants and cognitive constructions of social identities emphasized by earlier theoretical frameworks, transgender theory emphasizes the importance of physical embodiment in gender and sexual identity, as well as the integration of embodied experiences with the self and socially constructed aspects of identity through the lived experiences of those with fluid, often intersecting identities. The present paper considers important recent topics in research on transgender identities through the lens of this theory, including embodiment in understanding fluid gender and sexual identities, the intersectionality of multiple oppressed social identities, barriers to healthcare for transgender individuals, and ethical issues with regard to social policies impacting transgender individuals and with regard to media portrayals of and research on such individuals.

A Protocol for Mitotic Metaphase Chromosome Count Using Shoot Meristematic Tissues of Mulberry Tree Species.

Studies on chromosomal status are a fundamental aspect of plant cytogenetics and breeding because changes in number, size, and shape of chromosomes determine plant physiology/performance. Despite its significance, the classical cytogenetic study is now frequently avoided because of its tedious job. In general, root meristems are used to study the mitotic chromosome number, even though the use of root tips was restricted because of sample availability, processing, and lack of standard protocols. Moreover, to date, a protocol using shoot tips to estimate chromosome number has not yet been achieved for tree species' germplasm with a large number of accessions, like mulberry (Morusspp.). Here, we provide a step-by-step, economically feasible protocol for the pretreatment, fixation, enzymatic treatment, staining, and squashing of meristematic shoot tips. The protocol is validated with worldwide collections of 200 core set accessions with a higher level of ploidy variation, namely diploid (2n = 2x = 28), triploid (2n = 3x = 42), tetraploid (2n = 4x = 56), hexaploid (2n = 6x = 84), and decosaploid (2n = 22x = 308) belonging to nine species of Morus spp. Furthermore, accession from each ploidy group was subjected to flow cytometry (FCM) analysis for confirmation. The present protocol will help to optimize metaphase plate preparation and estimation of chromosome number using meristematic shoot tips of tree species regardless of their sex, location, and/or resources.

Early Post-Vaccination Gene Signatures Correlate With the Magnitude and Function of Vaccine-Induced HIV Envelope-Specific Plasma Antibodies in Infant Rhesus Macaques.

A better understanding of the impact of early innate immune responses after vaccine priming on vaccine-elicited adaptive immune responses could inform rational design for effective HIV vaccines. The current study compared the whole blood molecular immune signatures of a 3M-052-SE adjuvanted HIV Env protein vaccine to a regimen combining the adjuvanted Env protein with simultaneous administration of a modified Vaccinia Ankara vector expressing HIV Env in infant rhesus macaques at days 0, 1, and 3 post vaccine prime. Both vaccines induced a rapid innate response, evident by elevated inflammatory plasma cytokines and altered gene expression. We identified 25 differentially-expressed genes (DEG) on day 1 compared to day 0 in the HIV protein vaccine group. In contrast, in the group that received both the Env protein and the MVA-Env vaccine only two DEG were identified, implying that the MVA-Env modified the innate response to the adjuvanted protein vaccine. By day 3, only three DEG maintained altered expression, indicative of the transient nature of the innate response. The DEG represented immune pathways associated with complement activation, type I interferon and interleukin signaling, pathogen sensing, and induction of adaptive immunity. DEG expression on day 1 was correlated to Env-specific antibody responses, in particular antibody-dependent cytotoxicity responses at week 34, and Env-specific follicular T helper cells. Results from network analysis supported the interaction of DEG and their proteins in B cell activation. These results emphasize that vaccine-induced HIV-specific antibody responses can be optimized through the modulation of the innate response to the vaccine prime.

Microscopic nuclei classification, segmentation, and detection with improved deep convolutional neural networks (DCNN).

BACKGROUND: Nuclei classification, segmentation, and detection from pathological images are challenging tasks due to cellular heterogeneity in the Whole Slide Images (WSI). METHODS: In this work, we propose advanced DCNN models for nuclei classification, segmentation, and detection tasks. The Densely Connected Neural Network (DCNN) and Densely Connected Recurrent Convolutional Network (DCRN) models are applied for the nuclei classification tasks. The Recurrent Residual U-Net (R2U-Net) and the R2UNet-based regression model named the University of Dayton Net (UD-Net) are applied for nuclei segmentation and detection tasks respectively. The experiments are conducted on publicly available datasets, including Routine Colon Cancer (RCC) classification and detection and the Nuclei Segmentation Challenge 2018 datasets for segmentation tasks. The experimental results were evaluated with a five-fold cross-validation method, and the average testing results are compared against the existing approaches in terms of precision, recall, Dice Coefficient (DC), Mean Squared Error (MSE), F1-score, and overall testing accuracy by calculating pixels and cell-level analysis. RESULTS: The results demonstrate around 2.6% and 1.7% higher performance in terms of F1-score for nuclei classification and detection tasks when compared to the recently published DCNN based method. Also, for nuclei segmentation, the R2U-Net shows around 91.90% average testing accuracy in terms of DC, which is around 1.54% higher than the U-Net model. CONCLUSION: The proposed methods demonstrate robustness with better quantitative and qualitative results in three different tasks for analyzing the WSI.

Mitochondrial DNA based diversity studies reveal distinct and substructured populations of pearlspot, Etroplus suratensis (Bloch, 1790) in Indian waters.

Pearlspot (Etroplus suratensis) is one of the most commercially important brackish water fish species widely found along the coastal regions of peninsular India and Sri Lanka. Pearlspot is known for its tender flesh, delectable taste, culinary tourism and highyielding market value. Information on the genetic makeup of stocks/populations is extremely vital as it forms the basis for future genetic studies. For this, we utilized ATPase6/8 genes of mtDNA of pearlspot populations collected from nine different locations ranging from Ratnagiri in Maharashtra state on the west coast to Chilika in Odisha on the east coast. Sequence analyses of these genes revealed 33 polymorphic sites, which include 17 singleton and 16 parsimony informative sites. Pair-wise genetic differentiation study (FST = 0.75) indicated significant (P<0.001) differences among all the pairs of stocks except those from Chilika and Nagayalanka. The spatial analysis of molecular variance (SAMOVA) significantly delineated the population into four groups (FCT = 0.69, P = 0.0001), namely northwest (Ratnagiri and Goa); southwest (Mangalore and lakes at Vembanad, Ashtamudi and Vellayani in Kerala); southeast (Pulicat in Tamil Nadu) and northeast (Chilika in Odisha and Nagayalanka in Andhra Pradesh). The above delineation is supported by clades of the phylogenetic tree and also the clusters of median joining haplotype network. The high haplotype diversity (0.84), low nucleotide diversity (0.003), and negative values of Tajima's D (-1.47) and Fu's Fs statistic (-14.89) are characteristic of populations having recently undergone demographic expansion. Mantel test revealed significant isolation by distance. The study identifies highly delineated structured populations with restricted gene flow. If such a stock is overfished, it is highly unlikely that it would recover through migration. For any future breeding programme in this species, it would be desirable to form a base population which incorporates the genetic material from all the locations so that we get a wide gene pool to select from.

A Deep Neural Network for Early Detection and Prediction of Chronic Kidney Disease.

Diabetes and high blood pressure are the primary causes of Chronic Kidney Disease (CKD). Glomerular Filtration Rate (GFR) and kidney damage markers are used by researchers around the world to identify CKD as a condition that leads to reduced renal function over time. A person with CKD has a higher chance of dying young. Doctors face a difficult task in diagnosing the different diseases linked to CKD at an early stage in order to prevent the disease. This research presents a novel deep learning model for the early detection and prediction of CKD. This research objectives to create a deep neural network and compare its performance to that of other contemporary machine learning techniques. In tests, the average of the associated features was used to replace all missing values in the database. After that, the neural network's optimum parameters were fixed by establishing the parameters and running multiple trials. The foremost important features were selected by Recursive Feature Elimination (RFE). Hemoglobin, Specific Gravity, Serum Creatinine, Red Blood Cell Count, Albumin, Packed Cell Volume, and Hypertension were found as key features in the RFE. Selected features were passed to machine learning models for classification purposes. The proposed Deep neural model outperformed the other four classifiers (Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Logistic regression, Random Forest, and Naive Bayes classifier) by achieving 100% accuracy. The proposed approach could be a useful tool for nephrologists in detecting CKD.

Delineating virulence of Vibrio campbellii: a predominant luminescent bacterial pathogen in Indian shrimp hatcheries.

Luminescent vibriosis is a major bacterial disease in shrimp hatcheries and causes up to 100% mortality in larval stages of penaeid shrimps. We investigated the virulence factors and genetic identity of 29 luminescent Vibrio isolates from Indian shrimp hatcheries and farms, which were earlier presumed as Vibrio harveyi. Haemolysin gene-based species-specific multiplex PCR and phylogenetic analysis of rpoD and toxR identified all the isolates as V. campbellii. The gene-specific PCR revealed the presence of virulence markers involved in quorum sensing (luxM, luxS, cqsA), motility (flaA, lafA), toxin (hly, chiA, serine protease, metalloprotease), and virulence regulators (toxR, luxR) in all the isolates. The deduced amino acid sequence analysis of virulence regulator ToxR suggested four variants, namely A123Q150 (AQ; 18.9%), P123Q150 (PQ; 54.1%), A123P150 (AP; 21.6%), and P123P150 (PP; 5.4% isolates) based on amino acid at 123rd (proline or alanine) and 150th (glutamine or proline) positions. A significantly higher level of the quorum-sensing signal, autoinducer-2 (AI-2, p = 2.2e-12), and significantly reduced protease activity (p = 1.6e-07) were recorded in AP variant, whereas an inverse trend was noticed in the Q150 variants AQ and PQ. The pathogenicity study in Penaeus (Litopenaeus) vannamei juveniles revealed that all the isolates of AQ were highly pathogenic with Cox proportional hazard ratio 15.1 to 32.4 compared to P150 variants; PP (5.4 to 6.3) or AP (7.3 to 14). The correlation matrix suggested that protease, a metalloprotease, was positively correlated with pathogenicity (p > 0.05) and negatively correlated (p < 0.05) with AI-2 and AI-1. The syntenic organization of toxS-toxR-htpG operon in V. campbellii was found to be similar to pathogenic V. cholerae suggesting a similar regulatory role. The present study emphasizes that V. campbellii is a predominant pathogen in Indian shrimp hatcheries, and ToxR plays a significant role as a virulence regulator in the quorum sensing-protease pathway. Further, the study suggests that the presence of glutamine at 150th position (Q150) in ToxR is crucial for the pathogenicity of V. campbellii.

Flow cytometry analysis of apoptotic progression and expression analysis of four apoptosis-related genes in Penaeus vannamei in response to white spot syndrome virus infection.

Flow cytometry analysis was carried out to detect the progression of apoptosis in haemocytes of WSSV infected Penaeus vannamei at different time-points (1.5 hpi, 18 hpi and 56 hpi). Apoptosis in haemocytes was found to increase with time of infectivity from 5.06 to 69.63%. Quantitative real-time PCR (qPCR) was used for the expression analysis of four apoptosis-related genes such as Death-associated protein 1, caspase-5, translationally controlled tumor protein, and cathepsin D. The evidence of apoptosis in haemocytes of P. vannamei was established as shown by significant increase in the percentage of late apoptotic cells due to WSSV infection in shrimp. The present study gives an insight to the apoptosis rate in a WSSV infected shrimp during the course of infection and the role of apoptosis related genes.

Closed-tube field-deployable loop-mediated isothermal amplification (LAMP) assay based on spore wall protein (SWP) for the visual detection of Enterocytozoon hepatopenaei (EHP).

Hepatopancreatic microsporidiosis (HPM) is an infectious shrimp disease caused by the microsporidian Enterocytozoon hepatopenaei (EHP). In recent years, the widespread occurrence of EHP poses a significant challenge to the shrimp aquaculture industry. Early, rapid and accurate diagnosis of EHP infection is very much essential for the control of HPM crop-related losses. Loop-mediated isothermal amplification (LAMP) is a robust, sensitive, cost-effective disease diagnostic technique. Here, we demonstrate an improved, simple, closed-tube, colorimetric EHP LAMP diagnostic assay. LAMP assay was illustrated with the specific EHP spore wall protein (SWP) gene primers. Naked eye visual detection of LAMP amplicons was achieved using Hydroxy naphthol blue (HNB) or Phenol red dye without opening the tubes. This LAMP assay is efficient in detecting the EHP pathogen in all clinical samples include shrimp hepatopancreas, FTA card samples, feces, pond water, and soil. Also, the elution of EHP DNA from FTA cards was demonstrated within 17 min using a simple dry bath. In clinical evaluation, the visual LAMP assay established 100% diagnostic sensitivity and 100% diagnostic specificity. The visual LAMP assay is rapid, can detect the EHP pathogen within 40 min using a simple dry bath, and does not require any expensive instruments and technical proficiency. In conclusion, this visual LAMP protocol is a user-friendly, specific assay that can be conceivably operated at the farm-site/ resource-limited settings by the farmer himself with simple equipment.

Phylogenetic relations and mitogenome-wide similarity metrics reveal monophyly of Penaeus sensu lato.

Splitting of the genus Penaeus sensu lato into six new genera based on morphological features alone has been controversial in penaeid shrimp taxonomy. Several studies focused on building phylogenetic relations among the genera of Penaeus sensu lato. However, they lack in utilizing full mitochondrial DNA genome of shrimp representing all the six controversial genera. For the first time, the present study targeted the testing of all the six genera of Penaeus sensu lato for phylogenetic relations utilizing complete mitochondrial genome sequence. In addition, the study reports for the first time about the complete mitochondrial DNA genome sequence of Fenneropenaeus indicus, an important candidate species in aquaculture and fisheries, and utilized it for phylogenomics. The maximum likelihood and Bayesian approaches were deployed to generate and comprehend the phylogenetic relationship among the shrimp in the suborder, Dendrobranchiata. The phylogenetic relations established with limited taxon sampling considered in the study pointed to the monophyly of Penaeus sensu lato and suggested collapsing of the new genera to a single genus. Further, trends in mitogenome-wide estimates of average amino acid identity in the order Decapoda and the genus Penaeus sensu lato supported restoration of the old genus, Penaeus, rather promoting the creation of new genera.

Abundance, community structure and diversity of nitrifying bacterial enrichments from low and high saline brackishwater environments.

The study reports diversity in nitrifying microbial enrichments from low (0·5-5‰) and high (18-35‰) saline ecosystems. Microbial community profiling of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) enrichments was analysed by sequencing 16S rRNA and was processed using Mothur pipeline. The α-diversity indices showed the richness of nitrifying bacterial consortia from the high saline environment and were clustering based on the source of the sample. AOB and NOB enrichments from both the environments showed diverse lineages of phyla distributed in both groups with 38 and 34 phyla from low saline and 53 and 40 phyla in high saline sources, respectively. At class level, α- and γ-proteobacteria were found to be more dominant in both the enrichments. AOBs and NOBs in enrichments from low saline environments were dominated by Nitrosomonadaceae, Gallionellaceae (Nitrotoga sp.) and Ectothiorhodospiraceae and Nitrospira, respectively. Though Chromatiaceae were present in both AOB and NOB enrichments, Nitrosoglobus and Nitrosococcus dominated the AOBs while NOBs were dominated by uncultured genera, whereas Rhizobiales were found in both the enrichments. AOBs and NOBs in enrichments from high saline environments were dominated by Nitrospira-like AOBs, Nitrosomonas and Nitrosococcus genera, whereas ammonia-oxidizing archaea (AOA) group included Nitrosopumilus and Nitrososphaera genera comprising and Nitrospirae, respectively. The majority of the genera obtained in both the salinities were found to be either uncultured or unclassified groups. Results of the study suggest that the AOB and NOB consortia have unique and diverse microbes in each of the enrichments, capable of functioning in aquaculture systems practised at different salinities (0-60 ppt).

Secretion of von Willebrand Factor and Suppression of ADAMTS-13 Activity by Markedly High Concentration of Ferritin.

Hyperferritinemia is associated with poor outcomes in critically ill patients with sepsis, hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndromes (MAS) and coronavirus disease 19 (COVID-19). Autopsies of hyperferritinemic patients that succumbed to either sepsis, HLH, MAS or COVID-19 have revealed disseminated microvascular thromboses with von Willebrand factor (VWF)-, platelets-, and/or fibrin-rich microthrombi. It is unknown whether high plasma ferritin concentration actively promotes microvascular thrombosis, or merely serves as a prognostic biomarker in these patients. Here, we show that secretion of VWF from human umbilical vein endothelial cells (HUVEC) is significantly enhanced by 100,000 ng/ml of recombinant ferritin heavy chain protein (FHC). Ferritin fraction that was isolated by size exclusion chromatography from the plasma of critically ill HLH patients promoted VWF secretion from HUVEC, compared to similar fraction from non-critically ill control plasma. Furthermore, recombinant FHC moderately suppressed the activity of VWF cleaving metalloprotease ADAMTS-13. These observations suggest that a state of marked hyperferritinemia could promote thrombosis and organ injury by inducing endothelial VWF secretion and reducing the ADAMTS-13 activity.