Abstract
Background
Though reinfection with SARS-CoV-2 is well documented, there remains uncertainty about the potential for more severe symptoms with reinfections compared to index infections.
...Methods
Patients who received SARS-CoV-2 PCR testing between March 1, 2020 and March 1, 2021 at New York City Health and Hospitals (NYC H+H) facilities and had two positive tests > =90 days apart were included in the analysis. Clinical and demographic data were extracted from the electronic medical record. Manual chart review was done to confirm symptomatology, assess COVID-19 related hospital admissions, and determine WHO disease severity. Patients were then classified as unlikely reinfection, possible reinfection, or probable reinfection based on symptomatology, PCR and antibody testing, and lack of alternative diagnoses. Patients were classified as “unable to be assessed” if symptomatology could not be assessed for both episodes of PCR positivity. Figure 1:Flow chart of selection process for study inclusionFigure 2:Reinfection Classification
Results
During our study timeframe, 1,255,584 unique patients received at least one SARS-CoV-2 PCR test, 265 of whom had two positive tests > =90 days apart. We categorized 20 patients as unable to be assessed, 28 as unlikely reinfection (1 persistent PCR positivity, 27 unlikely true infection at index or second PCR-positive episode), and 217 as possible or probable reinfection. Of the 217, at their index episode 79 had an asymptomatic infection (36.4%) and 17 were severe or critical (7.8%). At their second episode, 162 patients had an asymptomatic infection (74.7%), and 5 were severe or critical (2.3%).
Only 24 patients with possible/probable reinfection had a more severe COVID reinfection than index infection, and 20 of the 24 had asymptomatic index infections. Three patients were hospitalized at both episodes, and two deaths possibly attributable to COVID-19 reinfection were noted in this cohort. Figure 3:Change in WHO disease severity classification from index to second infection among probable/possible reinfection cases (n=217)
Red indicates increase in disease severity from index to reinfection (n=24), blue indicates decrease in disease severity from index to reinfection (n=100), white indicates no change (n=74) and gray indicates unable to assess disease severity at index or second infection (n=19).
Conclusion
COVID-19 reinfection was rare in a high incidence setting among patients tested at NYC H+H facilities. Disease severity was generally milder in reinfection, although severe and critical disease occurred in a small number of patients. These findings from earlier in the pandemic (presumably wild-type and alpha variant) provide data for comparison in understanding how reinfection is evolving with newer variants.
Disclosures
Carlos Salama, MD, Genentech: Advisor/Consultant Gabriel Cohen, MD, Daybreak Health: Advisor/Consultant|Daybreak Health: Board Member|Daybreak Health: Ownership Interest.
Background and purpose
Differentiation between acute flaccid myelitis (AFM) and Guillain–Barré syndrome (GBS) can be difficult, particularly in children. Our objective was to improve the diagnostic ...accuracy by giving recommendations based on a comparison of clinical features and diagnostic criteria in children with AFM or GBS.
Methods
A cohort of 26 children with AFM associated with enterovirus D68 was compared to a cohort of 156 children with GBS. The specificity of the Brighton criteria, used for GBS diagnosis, was evaluated in the AFM cohort and the specificity of the Centers for Disease Control and Prevention (CDC) AFM diagnostic criteria in the GBS cohort.
Results
Children with AFM compared to those with GBS had a shorter interval between onset of weakness and nadir (3 vs. 8 days, p < 0.001), more often had asymmetric limb weakness (58% vs. 0%, p < 0.001), and less frequently had sensory deficits (0% vs. 40%, p < 0.001). In AFM, cerebrospinal fluid leukocyte counts were higher, whereas protein concentrations were lower. Spinal cord lesions on magnetic resonance imaging were only found in AFM patients. No GBS case fulfilled CDC criteria for definite AFM. Of the AFM cases, 8% fulfilled the Brighton criteria for GBS, when omitting the criterion of excluding an alternate diagnosis.
Conclusions
Despite the overlap in clinical presentation, we found distinctive early clinical and diagnostic characteristics for differentiating AFM from GBS in children. Diagnostic criteria for AFM and GBS usually perform well, but some AFM cases may fulfill clinical diagnostic criteria for GBS. This underlines the need to perform diagnostic tests early to exclude AFM in children suspected of atypical GBS.
A child with acute onset flaccid weakness may pose a diagnostic challenge for clinicians, with both acute flaccid myelitis (AFM) and Guillain–Barré syndrome (GBS) included in the differential diagnosis. We provide distinguishing features and recommendations, which may help clinicians in making the right diagnosis. In cases of atypical GBS, the diagnosis of AFM needs to be excluded early in the disease course, as AFM may fulfill the current clinical, cerebrospinal fluid, and nerve conduction studies diagnostic criteria for GBS.
We provide a phylogenetic revision of the Pseudocyphellaria crocata complex in the Americas. Specimens traditionally identified as P. crocata, based on their cyanobacterial photobiont, yellow ...pseudocyphellae, at least partially white medulla, and yellow soralia or soralia-like structures, are shown to represent 13 distinct species, forming a monophyletic group divided into four large clades, three comprising one species each and one containing eight species, plus two taxa for which no molecular data are available. Seven species correspond to what was previously recognized as P. crocata and one to P. dozyana, whereas a further one is identified as the sorediate counterpart of the usually apotheciate taxon P. lechleri and another as a pseudosorediate morph of the usually phyllidiate species P. neglecta. Surprisingly, none of the species represents P. crocata s.str., which must therefore be excluded from the American lichen biota. The 13 recognized species include three species new to science and three new combinations: P. citrina (Gyeln.) Lücking, Moncada & S.Stenroos, comb. nov. bas.: Cyanisticta citrina Gyeln., nom. nov. pro Sticta citrina Pers. nom. illeg., P. desfontainii (Delise) Vain., P. deyi Lücking, sp. nov., P. dozyana (Mont. & Bosch) D.J.Galloway, P. epiflavoides (Gyeln.) Lücking, Farkas & Lőkös, comb. nov. bas.: Cyanisticta epiflavoides Gyeln., P. hawaiiensis H.Magn., P. hillii (C.W.Dodge) D.J.Galloway, P. holarctica McCune, Lücking & Moncada, sp. nov., P. lechleri (Müll. Arg.) Du Rietz, P. neglecta (Müll. Arg.) H.Magn., P. punctata Lendemer, Lücking & Moncada sp. nov., P. sandwicensis (Zahlbr.) Moncada & Lücking, comb. nov. bas.: Sticta crocata f. sandwicensis Zahlbr., and P. xanthosticta (Pers.) Moncada & Lücking. Based on sequenced specimens, a neotype is selected for P. citrina and epitypes for P. hawaiiensis, P. lechleri, P. sandwicensis and P. xanthosticta. A key to all sorediate or pseudosorediate species of this complex in the Americas is presented, and all species are described, discussed and illustrated.
VIP: A Python package for high-contrast imaging Christiaens, Valentin; Gonzalez, Carlos Alberto Gómez; Farkas, Ralf ...
Journal of open source software,
01/2023, Letnik:
8, Številka:
81
Journal Article, Web Resource
Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated ...with that antimicrobial.
A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed.
Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤ 4 mg/L) and 27 (9.8%) in the borderline MIC group (8-16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34-3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18-4.88, P = 0.96; OR = 0.47, 95% CI = 0.10-2.26, P = 0.35; OR = 1.48, 95% CI = 0.33-6.68, P = 0.6).
We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae.
The opportunistic pathogen Candida albicans has a single protein phosphatase Z (PPZ) candidate gene termed CaPPZ1, which shows significant allele variability. We demonstrate here that bacterially ...expressed CaPpz1 protein exhibits phosphatase activity which can be inhibited by recombinant Hal3, a known inhibitor of Saccharomyces cerevisiae Ppz1. Site-directed mutagenesis experiments based on natural polymorphisms allowed the identification of three amino acid residues that affect enzyme activity or stability. The expression of CaPPZ1 in ppz1 S. cerevisiae and pzh1 Schizosaccharomyces pombe cells partially rescued the salt and caffeine phenotypes of the deletion mutants. CaPpz1 also complemented the slt2 S. cerevisiae mutant, which is crippled in the mitogen-activated protein (MAP) kinase that mediates the cell wall integrity signalling pathway. Collectively, our results suggest that the orthologous PPZ enzymes have similar but not identical functions in different fungi. The deletion of the CaPPZ1 gene in C. albicans resulted in a mutant that was sensitive to salts such as LiCl and KCl, to caffeine, and to agents that affect cell wall biogenesis such as Calcofluor White and Congo red, but was tolerant to spermine and hygromycin B. Reintegration of the CaPPZ1 gene into the deletion mutant alleviated all of the mutant phenotypes tested. Thus CaPpz1 is involved in cation homeostasis, cell wall integrity and the regulation of the membrane potential of C. albicans. In addition, the germ tube growth rate, and virulence in the BALB/c mouse model, were reduced in the null mutant, suggesting a novel function for CaPpz1 in the yeast to hypha transition that may have medical relevance.
The highly conserved Asn136 is in close proximity to the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI)-specific
lipophilic pocket of human immunodeficiency virus type 1 (HIV-1) RT. ...Site-directed mutagenesis has revealed that the catalytic
activity of HIV-1 RT mutated at position Asn136 is heavily compromised. Only 0.07 to 2.1% of wild-type activity is retained,
depending on the nature of the amino acid change at position 136. The detrimental effect of the mutations at position 136
occurred when the mutated amino acid was present in the p51 subunit but not in the p66 subunit of the p51/p66 RT heterodimer.
All mutant enzymes could be inhibited by second-generation NNRTIs such as efavirenz. They were also markedly more sensitive
to the inactivating (denaturating) effect of urea than wild-type RT, and the degree of increased urea sensitivity was highly
correlated with the degree of (lower) catalytic activity of the mutant enzymes. Replacing wild-type Asn136 in HIV-1 RT with
other amino acids resulted in notably increased amounts of free p51 and p66 monomers. Our findings identify a structural/functional
role for Asn136 in stabilization of the RT p66/p51 dimer and provide hints for the rational design of novel NNRTIs or drugs
targeting either Asn136 in the β7âβ8 loop of p51 or its anchoring point on p66 (the peptide backbone of His96) so as to interfere
with the RT dimerization process and/or with the structural support that the p51 subunit provides to the p66 subunit and which
is essential for the catalytic enzyme activity.
Avian chorioallantoic membrane (CAM) has been used as a model to explore angiogenesis and to study the microvasculature of transplanted tissues. Because CAM provides a vascular bed, cells can be ...implanted, and their development can be monitored and modified. We used the CAM model to study the differentiation process of embryoid bodies (EBs) derived from mouse embryonic stem cells (ESCs) influenced by the CAM vascular bed. After EBs were incubated in CAM for 5 days, they underwent further differentiation and became tissue masses (TMs) of different morphologies from those that grew outside CAM. Immunohistochemical analysis of TMs demonstrated tissue-specific markers such as neurofilament light, CD34, collagen IV, cardiac myosin heavy chain (MHC), and cardiotin. Differentiated mouse blood vessels stained with anti-CD31 were found within the TMs, as well as blood vessels stained positive for QH1 and QCPN, markers for quail endothelial cells and perinuclear quail antigen, respectively. Quail erythrocytes inside mouse blood vessels suggested a connection between existing quail vessels and blood vessels growing inside the TMs as a result of EB differentiation. Therefore, CAM could be a suitable model to trigger and study the differentiation of EBs in close interaction with surrogate quail blood vessels.
► The structure of Aspergillus nidulans PpzA has been conserved. ► PpzA is functionally competent in heterologous yeast cells. ► However, PpzA affects neither salt tolerance nor cell integrity in A. ...nidulans. ► Rather, it is involved in oxidative stress signaling. ► Maintenance of normal oxidative stress tolerance is a novel function of fungal PPZ enzymes.
The genome of the filamentous fungus Aspergillus nidulans harbors the gene ppzA that codes for the catalytic subunit of protein phosphatase Z (PPZ), and the closely related opportunistic pathogen Aspergillus fumigatus encompasses a highly similar PPZ gene (phzA). When PpzA and PhzA were expressed in Saccharomyces cerevisiae or Schizosaccharomyces pombe they partially complemented the deleted phosphatases in the ppz1 or the pzh1 mutants, and they also mimicked the effect of Ppz1 overexpression in slt2 MAP kinase deficient S. cerevisiae cells. Although ppzA acted as the functional equivalent of the known PPZ enzymes its disruption in A. nidulans did not result in the expected phenotypes since it failed to affect salt tolerance or cell wall integrity. However, the inactivation of ppzA resulted in increased sensitivity to oxidizing agents like tert-butylhydroperoxide, menadione, and diamide. To demonstrate the general validity of our observations we showed that the deletion of the orthologous PPZ genes in other model organisms, such as S. cerevisiae (PPZ1) or Candida albicans (CaPPZ1) also caused oxidative stress sensitivity. Thus, our work reveals a novel function of the PPZ enzyme in A. nidulans that is conserved in very distantly related fungi.
Pharmacogenetic testing is becoming more common; however, very few quality control and other reference materials that cover alleles commonly included in such assays are currently available. To ...address these needs, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, have characterized a panel of 107 genomic DNA reference materials for five loci ( CYP2D6 , CYP2C19 , CYP2C9 , VKORC1 , and UGT1A1 ) that are commonly included in pharmacogenetic testing panels and proficiency testing surveys. Genomic DNA from publicly available cell lines was sent to volunteer laboratories for genotyping. Each sample was tested in three to six laboratories using a variety of commercially available or laboratory-developed platforms. The results were consistent among laboratories, with differences in allele assignments largely related to the manufacturer's assay design and variable nomenclature, especially for CYP2D6 . The alleles included in the assay platforms varied, but most were identified in the set of 107 DNA samples. Nine additional pharmacogenetic loci ( CYP4F2 , EPHX1 , ABCB1 , HLAB , KIF6 , CYP3A4 , CYP3A5 , TPMT , and DPD ) were also tested. These samples are publicly available from Coriell and will be useful for quality assurance, proficiency testing, test development, and research.
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