Acute extravascular hemolytic transfusion reaction due to anti-Kpa antibody missed by electronic crossmatch

AbstractBackgroundKpa antigen is a low incidence red blood cell antigen within the Kell system. Anti-Kpa alloantibody may be associated with acute and delayed hemolytic transfusion reactions.Case StudyWe report a case of a clinically significant acute extravascular hemolytic transfusion reaction mediated by previously unrecognized (and undetected) anti-Kpa alloantibody. This reaction occurred in a patient who met all criteria for electronic crossmatch, resulting in the transfusion of an incompatible red cell unit.ResultsPost-transfusion investigation showed the transfused red cell unit was crossmatch compatible at the immediate spin phase but was 3 + incompatible at the antiglobulin phase. No evidence of intravascular hemolysis was observed upon visual comparison of the pre- and post-transfusion peripheral blood plasma. Further testing showed the presence of anti-Kpa antibody. The clinical course of the patient included acute febrile and systemic reaction.ConclusionAcute extravascular hemolytic transfusion reaction may occur due to undetected anti-Kpa alloantibody. Various strategies for crossmatching are discussed in the context of antibodies to low incidence antigens

Application of light microscopical and ultrastructural immunohistochemistry in the study of goblet cell carcinoid in the appendix

<p>Abstract</p> <p>Background</p> <p>Goblet cell carcinoids appear less frequently in the appendix than do other carcinoids. In the presented work a case with a goblet cell carcinoid of the appendix is described.</p> <p>Methods</p> <p>Routine histological and histochemical methods were employed, with a combination of histochemistry and immunohistochemistry on one section and light and electron microscopical immunohistochemisty on paraffin-embedded material, were applied to identify the type of the carcinoid and to reveal the fine structure of cell types in the tumour nests of the appendix.</p> <p>Results</p> <p>During the biopsy of a patient who had undergone appendectomy, an infiltration with clusters of goblet cells in the submucosa of the appendix was found. After a second operation of right-sided hemicolectomy, similar clusters of goblet cells were detected in the muscle layers of the caecum. After 18 months the patient died from cirrhosis and had not developed metastases or any recurrence. Immunohistochemically the serotonin-, somatostatin-, chromogranin A- and synaptophysin-positive endocrine cells were basally attached to mucin-secreting cells. The combined staining revealed simultaneously present endocrine cells (chromogranin-A-positive) and mucin-secreting cells (PAS- or alcian blue-positive). The ultrastructural immunohistochemistry showed that chromogranin A-positive cells had discoid and pleomorphic granules and were located in tumour nests or as single cells in the appendiceal wall.</p> <p>Conclusion</p> <p>The combined histochemical and immunohistochemical procedure and the ultrastructural immunohistochemistry on archival material could contribute in clarifying the diagnosis of goblet cell carcinoid.</p

Charting the metabolic biogeography of the colorectum in cancer : challenging the right sided versus left sided classification

Objective: Colorectal cancer (CRC) is conventionally classified as right sided, left sided, and rectal cancer. Clinicopathological, molecular features and risk factors do not change abruptly along the colorectum, and variations exist even within the refined subsites, which may contribute to inconsistencies in the identification of clinically relevant CRC biomarkers. We generated a CRC metabolome map to describe the association between metabolites, diagnostic and survival heterogeneity in cancers of different subsites of the colorectum. Design: Utilizing 372 patient-matched tumor and normal mucosa tissues, liquid chromatography-mass spectrometry was applied to examine metabolomic profiles along seven subsites of the colorectum: cecum (n = 63), ascending colon (n = 44), transverse colon (n = 32), descending colon (n = 28), sigmoid colon (n = 75), rectosigmoid colon (n = 38), and rectum (n = 92). Results: 39 and 70 significantly altered metabolites (including bile acids, lysophosphatidylcholines and lysophosphatidylethanolamines) among tumors and normal mucosa, respectively, showed inter-subsite metabolic heterogeneity between CRC subsites. Gradual changes in metabolite abundances with significantly linear trends from cecum to rectum were observed: 23 tumor-specific metabolites, 30 normal mucosa-specific metabolites, and 15 metabolites in both tumor and normal mucosa, had concentration gradients across the colorectum, and is disease status dependent. The metabolites that showed a linear trend included bile acids, amino acids, lysophosphatidylcholines, and lysophosphatidylethanolamines. Comparison of tumors to patient-matched normal mucosa revealed metabolite changes exclusive to each subsite, thereby further highlighting differences in cancer metabolism across the 7 subsites of the colorectum. Furthermore, metabolites associated with survival were different and unique to each subsite. Finally, an interactive and publicly accessible CRC metabolome database was designed to enable access and utilization of this rich data resource (https://colorectal-cancer-metabolome.com/yale-university). Conclusions: Gradual changes exist in metabolite abundances from the cecum to the rectum. The association between patient survival and distinct metabolites with anatomic subsite of the colorectum, reveals differences between cancers across the colorectum. These inter-subsite metabolic heterogeneities enrich the current understanding and substantiate previous studies that have challenged the conventional classification of right-sided, left-sided, and rectal cancers, by identifying specific metabolites that offer new biological insights into CRC subsite heterogeneity. The database designed in this study will enable researchers to delve into granular information on the CRC metabolome, which until now has not been available

Measurement of neutrino and antineutrino neutral-current quasielasticlike interactions on oxygen by detecting nuclear deexcitation γ rays

Neutrino- and antineutrino-oxygen neutral-current quasielastic-like interactions are measured at Super-Kamiokande using nuclear de-excitation $\gamma$-rays to identify signal-like interactions in data from a $14.94 \ (16.35)\times 10^{20}$protons-on-target exposure of the T2K neutrino (antineutrino) beam. The measured flux-averaged cross sections on oxygen nuclei are$\langle \sigma_{\nu {\rm -NCQE}} \rangle = 1.70 \pm 0.17 ({\rm stat.}) ^{+ {\rm 0.51}}_{- {\rm 0.38}} ({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}$with a flux-averaged energy of 0.82 GeV and$\langle \sigma_{\bar{\nu} {\rm -NCQE}} \rangle = 0.98 \pm 0.16 ({\rm stat.}) ^{+ {\rm 0.26}}_{- {\rm 0.19}} ({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}$ with a flux-averaged energy of 0.68 GeV, for neutrinos and antineutrinos, respectively. These results are the most precise to date, and the antineutrino result is the first cross section measurement of this channel. They are compared with various theoretical predictions. The impact on evaluation of backgrounds to searches for supernova relic neutrinos at present and future water Cherenkov detectors is also discussed

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Measurement of the muon neutrino charged-current cross sections on water, hydrocarbon and iron, and their ratios, with the T2K on-axis detectors

We report a measurement of the flux-integrated νμ charged-current cross sections on water, hydrocarbon, and iron in the T2K on-axis neutrino beam with a mean neutrino energy of 1.5 GeV. The measured cross sections on water, hydrocarbon, and iron are σH2OCC=(0.840±0.010(stat.)+0.10−0.08(syst.))×10−38cm2/nucleon, σCHCC=(0.817±0.007(stat.)+0.11−0.08(syst.))×10−38cm2/nucleon, and σFeCC=(0.859±0.003(stat.)+0.12−0.10(syst.))×10−38cm2/nucleon, respectively, for a restricted phase space of induced muons: θμ0.4 GeV/c in the laboratory frame. The measured cross section ratios are σH2OCC/σCHCC=1.028±0.016(stat.)±0.053(syst.)⁠, σFeCC/σH2OCC=1.023±0.012(stat.)±0.058(syst.)⁠, and σFeCC/σCHCC=1.049±0.010(stat.)±0.043(syst.)⁠. These results, with an unprecedented precision for the measurements of neutrino cross sections on water in the studied energy region, show good agreement with the current neutrino interaction models used in the T2K oscillation analyses

Constraint on the matter-antimatter symmetry-violating phase in neutrino oscillations

The charge-conjugation and parity-reversal (CP) symmetry of fundamental particles is a symmetry between matter and antimatter. Violation of this CP symmetry was first observed in 19641, and CP violation in the weak interactions of quarks was soon established2. Sakharov proposed3 that CP violation is necessary to explain the observed imbalance of matter and antimatter abundance in the Universe. However, CP violation in quarks is too small to support this explanation. So far, CP violation has not been observed in non-quark elementary particle systems. It has been shown that CP violation in leptons could generate the matter–antimatter disparity through a process called leptogenesis4. Leptonic mixing, which appears in the standard model’s charged current interactions5,6, provides a potential source of CP violation through a complex phase δCP, which is required by some theoretical models of leptogenesis7,8,9. This CP violation can be measured in muon neutrino to electron neutrino oscillations and the corresponding antineutrino oscillations, which are experimentally accessible using accelerator-produced beams as established by the Tokai-to-Kamioka (T2K) and NOvA experiments10,11. Until now, the value of δCP has not been substantially constrained by neutrino oscillation experiments. Here we report a measurement using long-baseline neutrino and antineutrino oscillations observed by the T2K experiment that shows a large increase in the neutrino oscillation probability, excluding values of δCP that result in a large increase in the observed antineutrino oscillation probability at three standard deviations (3σ). The 3σ confidence interval for δCP, which is cyclic and repeats every 2π, is [−3.41, −0.03] for the so-called normal mass ordering and [−2.54, −0.32] for the inverted mass ordering. Our results indicate CP violation in leptons and our method enables sensitive searches for matter–antimatter asymmetry in neutrino oscillations using accelerator-produced neutrino beams. Future measurements with larger datasets will test whether leptonic CP violation is larger than the CP violation in quarks

Genetic and epigenetic events regulating cellular senescence and aging

Bibliography: p. 213-24