Should prophylactic thrombolysis be routine in clinical practice? Evidence from an autopsy case of septicemia

BACKGROUND: Central venous catheters provide easy access for intravenous infusion and nutrition, but they can bring about complications such as catheter-related infections. Infected central venous catheters often cause nosocomial bloodstream infections with high morbidity and mortality. However, most of the morphological data that have been published are derived from in vitro and in vivo studies and few reports of direct evidence obtained from patient-derived samples have been described. Here we present visual evidence of catheter-related candidemia. To our knowledge, this is the first reported conventional histopathological evidence of a Candida-infected intraluminal thrombus in a patient’s central venous catheter. CASE PRESENTATION: A 62-year-old Japanese female with obstructive jaundice, gastrointestinal bleeding, and liver metastasis from pancreatic head cancer was given an implantable subcutaneous central venous port for nutrition and chemotherapy administration. High fever ensued on day 16 after the central venous port insertion and blood cultures revealed Candida albicans. Although the patient was given 300 mg/day of fosfluconazole according to the suggestion of the infection control team, she died from respiratory failure. Postmortem computed tomography revealed findings consistent with acute respiratory distress syndrome, suggesting that the patient’s course was complicated by catheter-related sepsis. Autopsy revealed a subcutaneous abscess around the port, from which C. albicans was cultured. However, no catheter-adherent thrombus, thrombosis of the great central veins, or endocardial vegetations were detected in the patient. Histological analysis revealed scattered abscesses in several organs including lungs and kidneys. Hyaline membrane formation and Candida colonies were found in the lungs. The central venous port tube, together with the part of the subclavian vein into which it had been inserted, was involved in an intraluminal fibrin thrombus containing neutrophils and macrophages, indicating that the thrombus existed while the patient was alive. Histopathological examination following use of the periodic acid-Schiff reagent and the Grocott stain revealed scattered Candida in the thrombus. CONCLUSIONS: Prophylactic thrombolysis should be encouraged to prevent central venous catheter-related candidiasis in clinical practice

Tenascin C interacts with Ecto-5′-nucleotidase (eN) and regulates adenosine generation in cancer cells

Tenascin C is expressed in invasive human solid tumors; however its specific role in cancer biology remains obscure. Previously, we have found that ecto-5'-nucleotidase (eN) is a marker of ER (-) breast carcinoma and elevated expression correlates with invasive mesenchymal cell phenotype. To investigate for the potential relationship between eN and protein components of the extracellular matrix (ECM) we measured adenosine generation from AMP in cells incubated with soluble ECM proteins. We found that tenascin C was the only ECM component that strongly inhibited ecto-5'-nucleotidase (eN) activity in situ and adenosine generation from AMP (75% inhibition, p < 0.01). The inhibition was comparable to that induced by concanavalin A, a well-defined and strong inhibitor of eN. Resin immobilized tenascin C, but not collagen, and only weakly fibronectin, specifically and quantitatively bound cell-extracted eN. We further developed breast cancer cell line with reduced eN expression and tested changes in cell adhesion on different ECM. Breast cancer cells expressing reduced eN attached 56% weaker (p < 0.05) to immobilized tenascin C. This difference was not detected with other ECM proteins. Finally, control breast cancer cells migrated slower on tenascin C when compared with clone with reduced eN expression. These data suggest that eN is a novel and specific receptor for tenascin C and that the interaction between these proteins may influence cell adhesion and migration and also lead to decreased generation of local adenosine

Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report

BackgroundLeft ventricular noncompaction (LVNC) is a rare inherited cardiomyopathy with a broad phenotypic spectrum. The genotype-phenotype correlations in fetal-onset LVNC have not yet been fully elucidated. In this report, we present the first case of severe fetal-onset LVNC caused by maternal low-frequency somatic mosaicism of the novel myosin heavy chain 7 (MYH7) mutation.Case presentationA 35-year-old pregnant Japanese woman, gravida 4, para 2, with no significant medical or family history of genetic disorders, presented to our hospital. In her previous pregnancy at 33 years of age, she delivered a male neonate at 30 weeks of gestation with cardiogenic hydrops fetalis. Fetal echocardiography confirmed LVNC prenatally. The neonate died shortly after birth. In the current pregnancy, she again delivered a male neonate with cardiogenic hydrops fetalis caused by LVNC at 32 weeks of gestation. The neonate died shortly after birth. Genetic screening of cardiac disorder-related genes by next-generation sequencing (NGS) was performed which revealed a novel heterozygous missense MYH7 variant, NM_000257.3: c.2729A &gt; T, p.Lys910Ile. After targeted and deep sequencing by NGS, the same MYH7 variant (NM_000257.3: c.2729A &gt; T, p.Lys910Ile) was detected in 6% of the variant allele fraction in the maternal sequence but not in the paternal sequence. The MYH7 variant was not detected by conventional direct sequencing (Sanger sequencing) in either parent.ConclusionsThis case demonstrates that maternal low-frequency somatic mosaicism of an MYH7 mutation can cause fetal-onset severe LVNC in the offspring. To differentiate hereditary MYH7 mutations from de novo MYH7 mutations, parental targeted and deep sequencing by NGS should be considered in addition to Sanger sequencing

Tenascin C interacts with Ecto-5′-nucleotidase (eN) and regulates adenosine generation in cancer cells

Tenascin C is expressed in invasive human solid tumors; however its specific role in cancer biology remains obscure. Previously, we have found that ecto-5'-nucleotidase (eN) is a marker of ER (-) breast carcinoma and elevated expression correlates with invasive mesenchymal cell phenotype. To investigate for the potential relationship between eN and protein components of the extracellular matrix (ECM) we measured adenosine generation from AMP in cells incubated with soluble ECM proteins. We found that tenascin C was the only ECM component that strongly inhibited ecto-5'-nucleotidase (eN) activity in situ and adenosine generation from AMP (75% inhibition, p < 0.01). The inhibition was comparable to that induced by concanavalin A, a well-defined and strong inhibitor of eN. Resin immobilized tenascin C, but not collagen, and only weakly fibronectin, specifically and quantitatively bound cell-extracted eN. We further developed breast cancer cell line with reduced eN expression and tested changes in cell adhesion on different ECM. Breast cancer cells expressing reduced eN attached 56% weaker (p < 0.05) to immobilized tenascin C. This difference was not detected with other ECM proteins. Finally, control breast cancer cells migrated slower on tenascin C when compared with clone with reduced eN expression. These data suggest that eN is a novel and specific receptor for tenascin C and that the interaction between these proteins may influence cell adhesion and migration and also lead to decreased generation of local adenosine

Standing on their own two feet. The role of nursing education in the life stories of nurse teachers from Bangladesh

[eng] The nursing profession in Bangladesh has undergone substantial development over recent decades but still faces significant challenges. A remarkable gap has been described between the institutionally-accepted image of nursing as the provision of hands-on care and the small amount of time that nurses allocate to it, especially in government hospitals. The reasons for this contradiction have shown a complex interaction between historical, socioeconomic and cultural factors. These are mainly related to the conflict between the British-inherited curriculum, with a strong emphasis on basic care activities, social and gender norms, and longstanding discrimination against nurses in their institutional settings and society. This research aims to provide a theoretical analysis of the ways in which structural factors intersect with the professional and social experiences of a group of nurse teachers. The objectives of the thesis are to describe nurses’ views about nursing care and their profession, to discuss to what extent nursing education has been an empowering tool, and to analyse how the nurses’ socioeconomic background, personal experiences and life events have influenced their professional careers and their conceptualisation of nursing and care. A critical phenomenological analysis of the nurses’ life stories has been used, relating the stories to the broader history and political economy of nursing in Bangladesh. Twenty-two nurses were selected and interviewed over an eight-month fieldwork period, of which seven were selected as key informants. The discussion is mainly based on theoretical contributions from anthropology, practice theory, feminism and a critical analysis of nursing knowledge. A common rhetoric was found among the nurses: namely that nursing care has ‘deteriorated’. They tended to emphasise hands-on care and the ‘old’ apprenticeship model, while also approving moves towards a more professional model. Nursing care activities were understood as a mixture of service and management of the wards and patients, linked to a wish to ‘utilise’ the knowledge that they were continuously acquiring. Therefore, nursing education was broadly empowering in terms of knowledge, independence, and self-realization. Nevertheless, at some moments social and institutional discrimination made the m feel disempowered, frustrated and vulnerable. Even so, the nurses interviewed have achieved successful professional careers, together with a significant amount of social recognition. Without ignoring their outstanding individual capacities, the role that key people and institutions had in supporting them in their eagerness to learn has to be considered. Finally, the act of caring itself and the knowledge that it produces may also be a source of personal and collective agency. However, work is needed in order to create and maintain the necessary conditions for the caring experience to be empowering. This responsibility falls beyond the nursing field, as it involves structural changes, especially in terms of gender and class inequalities.[cat] La professió infermera a Bangladesh ha experimentat importants avenços en les últimes dècades, tot i que encara presenta reptes considerables. La imatge institucionalment acceptada de la infermeria com la provisió de cures i contacte continuat amb els pacients contrasta amb la poca dedicació de moltes infermeres a aquestes activitats, especialment en els hospitals públics. Aquesta contradicció s’explica per una complexa interacció entre factors històrics, socioeconòmics i culturals. Existeix un conflicte entre un pla d’estudis heretat de l’època colonial Britànica, amb un fort èmfasi en les activitats de cures bàsiques, les normes socials i de gènere, i la històrica discriminació de les infermeres en els seus entorns institucionals i socials. Aquesta tesi pretén teoritzar sobre les formes en què els factors estructurals s’interseccionen amb les experiències professionals i socials d’un grup de professores d’infermeria. Els objectius de la tesi són: descriure les visions de les infermeres sobre el concepte de cura i sobre la seva professió; discutir fins a quin punt l’educació en infermeria ha estat una eina empoderadora, i analitzar de quina manera el context socioeconòmic, experiències personals i esdeveniments vitals de les professores han influït en la seva carrera professional i en la seva conceptualització de les cures infermeres. La recerca ha realitzat una anàlisi fenomenològica crítica de les històries de vida de les professores d’infermeria, relacionant-les amb la història i economia política de la infermeria a Bangladesh. Vint infermeres van ser entrevistades durant un període de vuit mesos, entre les quals set professores van ser escollides com a informants clau. La discussió es basa principalment en les aportacions teòriques de l'antropologia, la teoria de la pràctica, el feminisme i l’anàlisi crítica del coneixement infermer. Les infermeres entrevistades sostenien, en general, que les cures d'infermeria s’havien ‘deteriorat’. Les seves narratives tendien a emfatitzar el ‘vell’ model d’aprenentatge pràctic, alhora que es valorava l’evolució cap a un model més professional. Les infermeres conceptualitzaven la cura com una barreja entre les nocions de servei i de gestió de les sales i dels pacients, juntament amb un desig d’utilitzar els coneixements que constantment adquiriren. Per tant, l’educació en infermeria ha estat en general empoderadora quant a coneixements, independència i sentit d’auto-realització. Tot i així, en certs moments, la discriminació social i institucional viscuda, els va fer sentir impotents, frustrades i vulnerables. Malgrat les dificultats, però, les infermeres d’aquesta tesi han aconseguit un exitós desenvolupament professional, així com un grau de reconeixement social considerable. Sense ignorar les seves notables capacitats individuals, cal considerar també el suport rebut per part de diferents persones i institucions en el seu constant desig de formar-se i aprendre. Finalment, l’acte de tenir cura i el coneixement que se’n deriva, són en si mateixos una font d’agència personal i col·lectiva. No obstant això, cal treballar per crear i mantenir les condicions necessàries perquè l’experiència cura sigui empoderadora. Aquesta és una responsabilitat que excedeix l’àmbit infermer, ja que implica canvis estructurals, especialment en relació a les desigualtats de gènere i classe

New radiosynthesis of 2-deoxy-2-[18F]flouroacetamido-D-glucopyranose and its evaluation as a bacterial infections imaging agent

Introduction: The diagnosis of infection and the ability to distinguish bacterial infection from nonbacterial inflammation by positronemission tomography (PET) have gained interest in recent years, but still few specific radiopharmaceuticals are available for use. In thisstudy, we developed a new radiosynthesis method of 2-deoxy-2-[18F]fluoroacetamido-D-glucopyranose ([18F]FAG) by applyingmicrowave irradiation and demonstrated that [18F]FAG could be a potential radiopharmaceutical to distinguish bacterial infection fromnonbacterial inflammation.Methods: 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-bromoacetamido-D-glucopyranose was used as precursor, and labeling was performed undermicrowave irradiation conditions followed by alkaline hydrolysis and high-performance liquid chromatography (HPLC) purification. In vitrouptake of [18F]FAG by Escherichia coli was performed. Tissue biodistribution of [18F]FAG was performed in mice. Moreover, PET imagingacquisition of E. coli infection and nonbacterial inflammation models was performed in rats. Tissue radiotracer-accumulated sites wereanalyzed by hematoxylin and eosin staining and anti&#8211;E.coli immunostaining.Results: The radiosynthesis of [18F]FAG was achieved with microwave irradiation, and the radiochemical yield was 9.7%+-2.8% end ofbombardment (EOB); the radiochemical purity was more than 98%, and the total synthesis time was 62 min. Compared with control group, invitro uptake of [18F]FAG by E. coli was significantly decrease in inhibition group (Pb.05). Biodistribution studies in mice showed rapidclearance of [18F]FAG from the animal body. [18F]FAG clearly visualized the infection areas but not nonbacterial inflammation areas in PETstudies. Quantitative analysis revealed that the uptake of [18F]FAG into infection areas was significantly higher than that of [18F]FAG intoinflammation areas (Pb.05). Histological analysis demonstrated the presence of bacterial cells at the sites of accumulation of [18F]FAG.Conclusions: Using 1,3,4,6-tetra-O-acetyl-2-deoxy-2-bromoacetamido-D-glucopyranose as a precursor, the new radiosynthesis method of[18F]FAG was achieved in fewer steps and with a shorter synthesis time than previously reported. Furthermore, [18F]FAG was able todistinguish bacterial infection from nonbacterial inflammation

Improved artificial intelligence discrimination of minor histological populations by supplementing with color-adjusted images

Abstract Despite the dedicated research of artificial intelligence (AI) for pathological images, the construction of AI applicable to histopathological tissue subtypes, is limited by insufficient dataset collection owing to disease infrequency. Here, we present a solution involving the addition of supplemental tissue array (TA) images that are adjusted to the tonality of the main data using a cycle-consistent generative adversarial network (CycleGAN) to the training data for rare tissue types. F1 scores of rare tissue types that constitute < 1.2% of the training data were significantly increased by improving recall values after adding color-adjusted TA images constituting < 0.65% of total training patches. The detector also enabled the equivalent discrimination of clinical images from two distinct hospitals and the capability was more increased following color-correction of test data before AI identification (F1 score from 45.2 ± 27.1 to 77.1 ± 10.3, p < 0.01). These methods also classified intraoperative frozen sections, while excessive supplementation paradoxically decreased F1 scores. These results identify strategies for building an AI that preserves the imbalance between training data with large differences in actual disease frequencies, which is important for constructing AI for practical histopathological classification

Additional file 1: of Newly recognized cerebral infarctions on postmortem imaging: a report of three cases with systemic infectious disease

Timeline of Case 1. (DOCX 20 kb