Analysis allowed the identification of previously undetected factors in tears of VKC patients (i.e., MMP-3 and MMP-10) and confirmed the presence of a high expression of multiple MMPs, growth factors ...and cytokines that contribute to the pathogenesis of conjunctival allergic inflammation.
Objective
To test the hypothesis that the formation of ectopic germinal center (GC)–like structures in Sjögren's syndrome (SS) is associated with the ectopic expression of the constitutive lymphoid ...tissue–homing chemokines B cell–attracting chemokine 1 (BCA‐1; or, CXCL13) and stromal cell–derived factor 1 (SDF‐1; or, CXCL12).
Methods
Immunohistochemical and immunofluorescence analysis was used to determine the expression of the constitutive chemokines BCA‐1 (CXCL13) and SDF‐1 (CXCL12) in salivary glands from 5 SS patients and 3 non‐SS patients. In addition, the expression of their respective receptors (CXCR5 and CXCR4) was examined on infiltrating lymphocytes. Human tonsil was used as a positive control for secondary lymphoid tissue.
Results
BCA‐1 (CXCL13) was expressed within lymphoid aggregates in SS, which shared many structural features with GCs in tonsil. BCA‐1 (CXCL13) was completely absent in control biopsy samples from patients who did not have SS. High levels of BCA‐1 (CXCL13) were also found on endothelial cells in salivary glands from SS patients. Diseased SS tissue was infiltrated by CXCR5‐expressing B cells which organized into GC‐like clusters. In complete contrast, SDF‐1 (CXCL12), a constitutive chemokine involved in leukocyte retention within lymphoid tissue, was expressed by epithelial cells in both diseased and control samples. The chemokine receptor for SDF‐1, CXCR4, was expressed on T cells that accumulated in a periductal distribution in diseased tissue.
Conclusion
The ectopic expression of BCA‐1 (CXCL13) on endothelial cells and within GC‐like structures, together with the strong expression of SDF‐1 (CXCL12) on ductal epithelial cells, is a unique feature of inflamed glands in SS. By creating a local microenvironment supportive of focal B cell aggregation and differentiation, with structural features that are remarkably similar to GCs, BCA‐1 (CXCL13) and SDF‐1 (CXCL12) may contribute to the excessive production of high‐affinity, class‐switched autoantibodies and to the high incidence of B cell lymphomas classically associated with SS.
Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of ...cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic.
We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention PCI, PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs.
Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37–43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13–20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38–46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12–29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29–45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2–9) in 2019 to 3 days (1–5) by the end of March, 2020.
Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses.
UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.
Objective We sought to report on laboratory and clinical experience following 6 months of clinical implementation of a single-nucleotide polymorphism–based noninvasive prenatal aneuploidy test in ...high- and low-risk women. Study Design All samples received from March through September 2013 and drawn ≥9 weeks’ gestation were included. Samples that passed quality control were analyzed for trisomy 21, trisomy 18, trisomy 13, and monosomy X. Results were reported as high or low risk for fetal aneuploidy for each interrogated chromosome. Relationships between fetal fraction and gestational age and maternal weight were analyzed. Follow-up on outcome was sought for a subset of high-risk cases. False-negative results were reported voluntarily by providers. Positive predictive value (PPV) was calculated from cases with an available prenatal or postnatal karyotype or clinical evaluation at birth. Results Samples were received from 31,030 patients, 30,705 met study criteria, and 28,739 passed quality-control metrics and received a report detailing aneuploidy risk. Fetal fraction correlated positively with gestational age, and negatively with maternal weight. In all, 507 patients received a high-risk result for any of the 4 tested conditions (324 trisomy 21, 82 trisomy 18, 41 trisomy 13, 61 monosomy X; including 1 double aneuploidy case). Within the 17,885 cases included in follow-up analysis, 356 were high risk, and outcome information revealed 184 (51.7%) true positives, 38 (10.7%) false positives, 19 (5.3%) with ultrasound findings suggestive of aneuploidy, 36 (10.1%) spontaneous abortions without karyotype confirmation, 22 (6.2%) terminations without karyotype confirmation, and 57 (16.0%) lost to follow-up. This yielded an 82.9% PPV for all aneuploidies, and a 90.9% PPV for trisomy 21. The overall PPV for women aged ≥35 years was similar to the PPV for women aged <35 years. Two patients were reported as false negatives. Conclusion The data from this large-scale report on clinical application of a commercially available noninvasive prenatal test suggest that the clinical performance of this single-nucleotide polymorphism–based noninvasive prenatal test in a mixed high- and low-risk population is consistent with performance in validation studies.
The origin of autoreactive CD4-CD8- T cells is largely unknown. In TCR transgenic (Tg) mice expressing the cognate class I MHC antigen, CD4-CD8- T cells differed depending on characteristics of ...Tg-TCR/antigen interaction. Tg-TCR/CD3lo CD4-CD8- T cells expressing the NK1.1 marker were observed only for a Tg-TCR whose stimulation by antigen was independent of CD8. Unlike normal T cells, which have essentially TCR-associated zeta homodimers, these cells had a high proportion of TCR-associated zeta-Fc epsilon RI gamma heterodimers. They were also characterized by an unusually high content of Fc epsilon RI gamma mRNA and low content of mRNA encoding CD3 epsilon, CD3 gamma, CD3 delta, and zeta. Based on their phenotype and selection requirements, it is proposed that CD4-CD8- thymic precursor cells can be driven along the CD4-CD8-NK1.1+ pathway following coreceptor-independent TCR signaling at an intrathymic stage when Fc epsilon RI gamma and CD3 components are coexpressed.
A simple method to determine Lewis electron dot structures and formal charges without a need to sum all of the valence electrons, reorganize electron pairs, draw and pair up individual electrons, or ...remember a formal charge formula is described. The formal charge is determined by the group number (number of valence electrons) and the number of bonds, with the sum of formal charges then being equal to the total charge. This leads directly to a valid Lewis structure. The facility of the procedure allows the student to focus more on the chemical aspects of deciding which valid Lewis structure (or structures) is the correct or most important one.
Objective We sought to determine the ability of single-nucleotide polymorphism–based noninvasive prenatal testing (NIPT) to identify triploid, unrecognized twin, and vanishing twin pregnancies. Study ...Design The study included 30,795 consecutive reported clinical cases received for NIPT for fetal whole-chromosome aneuploidies; known multiple gestations were excluded. Cell-free DNA was isolated from maternal blood samples, amplified via 19,488-plex polymerase chain reaction, and sequenced. Sequencing results were analyzed to determine fetal chromosome copy number and to identify the presence of additional fetal haplotypes. Results Additional fetal haplotypes, indicative of fetal triploidy, vanishing twin, or undetected twin pregnancy, were identified in 130 (0.42%) cases. Clinical confirmation (karyotype for singleton pregnancies, ultrasound for multifetal pregnancies) was available for 58.5% (76/130) of cases. Of the 76 cases with confirmation, 42.1% were vanishing twin, 48.7% were viable twin, 5.3% were diandric triploids, and 3.9% were nontriploid pregnancies that lacked evidence of co-twin demise. One pregnancy had other indications suggesting triploidy but lacked karyotype confirmation. Of the 5 vanishing twin cases with a known date of demise, 100% of losses occurred in the first trimester; up to 8 weeks elapsed between loss and detection by NIPT. Conclusion This single-nucleotide polymorphism–based NIPT successfully identified vanished twin, previously unrecognized twin, and triploid pregnancies. As vanishing twins are more likely to be aneuploid, and undetected residual cell-free DNA could bias NIPT results, the ability of this method to identify additional fetal haplotypes is expected to result in fewer false-positive calls and prevent incorrect fetal sex calls.
A discrete dichloride ion pair in the form of a monohydrate, Cl
2
(H
2
O)
2−
, was isolated using the triaminocyclopropenium cation C
3
(NHex
2
)(N(CH
2
CF
3
)
2
)
2
+
. Although this ion pair is ...calculated to be unstable in the gas phase, the ionic lattice and weak CH-Cl hydrogen bonds assist the stabilization of the cluster. The D
2
O and HDO isotopomers were also prepared and characterized.
Calculations suggest that at least two waters are required to form a chloride-chloride ion pair. In fact, only one is required.
Solid-state packing arrangements in a series of five POMs shows that the melting point and solubility properties are dependent on the nature of the packing, with the tetra-anionic POMs having lower ...melting points and greater solubility than the tri-anionic POMs due to the increase in cation–cation interactions.
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Five new Keggin polyoxometalate (POM) salts were prepared with the tris(dihexylamino)cyclopropenium cation C3(NHex2)3+ in an effort to investigate and understand the impact of combining triaminocyclopropenium (TAC) cations with POMs on their thermochemical and thermophysical properties. The tri-anions PM12O403– (M = Mo, W) have high melting salts (Tm = 140 and 129 °C, respectively), whereas the tetra-anions PVMo11O404– and HPV2M10O404– (M = Mo, W), despite the increased electrostatic charge, have lower and very similar melting points (Tm ∼ 82 °C). The solid-state structures are all very similar, however, the tetra-anionic salts have a double layer of cations (compared to a single layer for the tri-anionic salts) and the electrostatic repulsion between these layers is likely responsible for the lower and similar melting points, as well as their increased solubility in non-polar solvents. The salts were also characterised by TGA, DSC, solubility studies, X-ray crystallography, NMR and infrared spectroscopy.
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