Correction: Thrombotic and bleeding events,mortality, and anticoagulant use among 546,656 hospitalized patients with COVID‑19 in the United States: a retrospective cohort study

Journal of Thrombosis and Thrombolysis -     

Optimization of immunohistochemical detection of collagen type II in osteochondral sections by comparing decalcification and antigen retrieval agent combinations

Bone containing tissues such as osteochondral joint are resistant to routine tissue processing, therefore require decalcification. This technique causes removal of mineral salts, but in the process may macerate the organic tissue, hence the need for tissue fixation. Such severe processing demands careful antigen retrieval to necessitate optimal staining. The aim of our study was to compare five different antigen retrieval protocols (heat retrieval and protein digestion) following decalcification of rabbit knee joints using two different techniques (20% formic acid and 10% ethylenediamine-tetra acetic acid: EDTA). Osteochondral sections were compared based on time required for decalcification, ease of sectioning, morphological integrity using HE staining and antigen preservation (Collagen type II) using immunohistochemistry. The two decalcification solutions did not impair the tissue morphology and ease of sectioning. Joints processed with formic acid decalcified four times faster than EDTA. Among the five antigen retrieval approaches, maximal collagen II uptake with minimal nonspecific staining was found with protein digestion (pronase and hyaluronidase) in both formic acid and EDTA sections. For osteo-chondral sections, we recommend using 10% EDTA for decalcification and pronase plus hyaluronidase for antigen retrieval if maintaining tissue morphology is crucial, whereas if time is of the essence, 20% FA with pronase plus hyaluronidase is the faster option while still preserving structural integrity. Clin. Anat. 33:343–349, 2020. © 2019 Wiley Periodicals, Inc.     

Slipped upper femoral epiphysis with hemophilia A

A 13-year-old boy who had hemophilia A was reported with pain in the left thigh and hip on walking. He had no history of trauma. Severe hemophilia A is diagnosed with a Factor VIII level of <1 iu/dl. The presumptive diagnosis was that of a spontaneous bleed into the hip joint. Factor VIII mutational analysis revealed a C to G substitution at nucleotide 6683 which results in a cystine change at codon 2194. However, the symptoms persisted and an X-ray demonstrated the presence of an acute on chronic slip of the upper femoral epiphysis. The patient was transferred to the center treating his hemophilia where the hip was pinned in situ under cover with Factor VIII. This case demonstrates the need to be aware of a possible traumatic diagnosis of hip pain in a hemophiliac child with a longstanding history of spontaneous bleeding into joints.     

The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.     

Intracranial mycotic aneurysm due to Aspergillus species.

BACKGROUND: Intracranial true mycotic aneurysms are uncommon and usually fatal. We report two patients with basilar mycotic aneurysms due to Aspergillus species following surgical interventions. Both patients had subarachnoid hemorrhage and diagnosis was made at autopsy only. The literature regarding etiology, clinical presentation, predisposing conditions and outcome of intracranial true mycotic aneurysms is reviewed from 1990-2005. A high index of clinical suspicion with prompt diagnosis and early treatment may improve patient outcome.     

Nucleoside peptides. 10. Synthesis and T-cell immunostimulatory properties of certain peptide derivatives of 6-azacadeguomycin

Several amino acid and peptide conjugates of 6-azacadeguomycin (6-amino-1-beta-D-ribofuranosyl-4,5-dihydro-4-oxopyrazolo[3,4-d]py rimidine- 3-carboxylic acid, 2) have been prepared in good yields, via a two-step procedure involving 1-hydroxybenzotriazole and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride mediated coupling of 2 with an appropriately protected amino acid or peptide, followed by ammonolysis. Thus, condensation of 2 with L-phenylalanine methyl ester, glycine ethyl ester, and L-glutamic acid diethyl ester gave the corresponding protected linear nucleoside peptides (3, 5 and 7, respectively). Subsequent ammonolysis of 3, 5 and 7 furnished L-phenylalanine amide (4), glycine amide (6) and L-glutamic acid diamide (8) conjugates of 6-azacadeguomycin, respectively. Saponification of 7 gave the corresponding L-glutamic acid derivative 9. A similar coupling of 2 with L-phenylalaninyl-N epsilon-nitro-L-arginine methyl ester trifluoroacetate and subsequent ammonolysis (after catalytic hydrogenation) gave L-phenylalaninyl-L-arginine amide conjugate (12) of 6-azacadeguomycin. Compounds 2, 4, 6, 8, 9, and 12 were evaluated for their ability to potentiate T-cell responses to plant mitogens, in comparison with cadeguomycin (1). Compounds 4, 6, and 9 exhibited an increase in the T-cell proliferation in a dose-dependent manner.     

Host immunity to mosquitoes: effect of antimosquito antibodies on Anopheles tessellatus and Culex quinquefasciatus (Diptera: Culicidae).

Rabbit antibodies to antigens derived from the tissues of sugar-fed Anopheles tessellatus Theobald were fed to An. tessellatus and Culex quinquefasciatus Say in blood meals. These antibodies tended to reduce the number of eggs produced by An. tessellatus, but had no effect on the fecundity of Cx. quinquefasciatus. Ingestion of the rabbit antibodies did not detectably affect the mortality of An. tessellatus but increased the mortality of Cx. quinquefasciatus. The results provide preliminary evidence for the potential of antimosquito antibodies to disrupt the physiology of mosquito vectors and indicate the need for further studies with high-titer, monospecific antibodies against the relevant target antigens.