Design of 2D Time-Varying Vector Fields

published_or_final_versio

Antimicrobial susceptibility and serotype distribution of Streptococcus agalactiae rectovaginal colonising isolates from pregnant women at a tertiary hospital in Pretoria, South Africa: An observational descriptive study

Background. Streptococcus agalactiae or group B streptococcus (GBS) is a significant cause of neonatal sepsis. Intrapartum antibiotic prophylaxis is recommended for pregnant women identified to be rectovaginally colonised between 34 and 37 weeks’ gestational age to decrease the risk of invasive disease in their newborns. An effective multivalent GBS vaccine may prevent a broader scope of GBS-associated diseases, such as GBS early-onset disease, GBS late-onset disease, spontaneous abortion, stillbirth and maternal bacteraemia. Serotype distribution of GBS isolates is essential to determine the efficacy of such a vaccine.Objectives. To investigate serotype distribution and antimicrobial susceptibility patterns of GBS isolates cultured from rectovaginal specimens during pregnancy.Methods. Sixty-nine archived maternal colonising isolates were tested against penicillin, erythromycin, clindamycin, vancomycin and levofloxacin. Minimum inhibitory concentration testing was performed using the ETEST method. Serotyping was performed by the latex agglutination method.Results. The most common serotypes detected were Ia (54%), III (20%), V (16%), II (6%), IV (2%) and Ib (1%). All isolates were fully susceptible to penicillin, vancomycin and levofloxacin. Eight (11%) and 50 (56%) isolates showed intermediate resistance to erythromycin and clindamycin, respectively, and 1 isolate was resistant to erythromycin. The macrolide-lincosamide-streptogramin B (MLSB) phenomenon was noted in 3 (4%) of the isolates.Conclusions. GBS-colonising isolates remain susceptible to penicillin, which remains the drug of choice for intrapartum antibiotic prophylaxis and treatment of invasive disease in newborns. Macrolides should only be used if clinically indicated due to the high prevalence of intermediate resistance. A pentavalent GBS vaccine currently in phase I trials should provide coverage for 97% of the isolates identified in this study

Antimicrobial susceptibility and serotype distribution of Streptococcus agalactiae rectovaginal colonising isolates from pregnant women at a tertiary hospital in Pretoria, South Africa : an observational descriptive study

BACKGROUND. Streptococcus agalactiae or group B streptococcus (GBS) is a significant cause of neonatal sepsis. Intrapartum antibiotic prophylaxis is recommended for pregnant women identified to be rectovaginally colonised between 34 and 37 weeks’ gestational age to decrease the risk of invasive disease in their newborns. An effective multivalent GBS vaccine may prevent a broader scope of GBS-associated diseases, such as GBS early-onset disease, GBS late-onset disease, spontaneous abortion, stillbirth and maternal bacteraemia. Serotype distribution of GBS isolates is essential to determine the efficacy of such a vaccine. OBJECTIVES. To investigate serotype distribution and antimicrobial susceptibility patterns of GBS isolates cultured from rectovaginal specimens during pregnancy. METHODS. Sixty-nine archived maternal colonising isolates were tested against penicillin, erythromycin, clindamycin, vancomycin and levofloxacin. Minimum inhibitory concentration testing was performed using the ETEST method. Serotyping was performed by the latex agglutination method. RESULTS. The most common serotypes detected were Ia (54%), III (20%), V (16%), II (6%), IV (2%) and Ib (1%). All isolates were fully susceptible to penicillin, vancomycin and levofloxacin. Eight (11%) and 50 (56%) isolates showed intermediate resistance to erythromycin and clindamycin, respectively, and 1 isolate was resistant to erythromycin. The macrolide-lincosamide-streptogramin B (MLSB) phenomenon was noted in 3 (4%) of the isolates. CONCLUSIONS. GBS-colonising isolates remain susceptible to penicillin, which remains the drug of choice for intrapartum antibiotic prophylaxis and treatment of invasive disease in newborns. Macrolides should only be used if clinically indicated due to the high prevalence of intermediate resistance. A pentavalent GBS vaccine currently in phase I trials should provide coverage for 97% of the isolates identified in this study.The National Health Laboratory Service (NHLS) and the Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg.http://www.samj.org.zaam2021Medical Microbiolog

AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2

Background: Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determine the effect of subsequent COVID-19 vaccination. Methods: Using a prospective cohort design, we recruited adults with prior laboratory-confirmed mild/moderate COVID-19 in Blantyre, Malawi, and followed them up for 270 days (n = 52). A subset of whom subsequently received a single dose of the AstraZeneca COVID-19 vaccine (ChAdOx nCov-19) (n = 12). We measured the serum concentrations of anti-Spike and receptor-binding domain (RBD) IgG antibodies using a Luminex-based assay. Anti-RBD antibody cross-reactivity across SARS-CoV-2 variants of concern (VOC) was measured using a haemagglutination test. A pseudovirus neutralisation assay was used to measure neutralisation titres across VOCs. Ordinary or repeated measures one-way ANOVA was used to compare log10 transformed data, with p value adjusted for multiple comparison using Šídák's or Holm-Šídák's test. Results: We show that neutralising antibodies wane within 6 months post mild/moderate SARS-CoV-2 infection (30–60 days vs. 210–270 days; Log ID50 6.8 vs. 5.3, p = 0.0093). High levels of binding anti-Spike or anti-RBD antibodies in convalescent serum were associated with potent neutralisation activity against the homologous infecting strain (p < 0.0001). A single dose of the AstraZeneca COVID-19 vaccine following mild/moderate SARS-CoV-2 infection induced a 2 to 3-fold increase in anti-Spike and -RBD IgG levels 30 days post-vaccination (both, p < 0.0001). The anti-RBD IgG antibodies from these vaccinated individuals were broadly cross-reactive against multiple VOCs and had neutralisation potency against original D614G, beta, and delta variants. Conclusions: These findings show that the AstraZeneca COVID-19 vaccine is an effective booster for waning cross-variant antibody immunity after initial priming with SARS-CoV-2 infection. The potency of hybrid immunity and its potential to maximise the benefits of COVID-19 vaccines needs to be taken into consideration when formulating vaccination policies in sub-Saharan Africa, where there is still limited access to vaccine doses

Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: implications for drug development

The development of drugs to inhibit glioblastoma (GBM) growth requires reliable preclinical models. To date, proteomic level validation of widely used patient-derived glioblastoma xenografts (PDGX) has not been performed. In the present study, we characterized 20 PDGX models according to subtype classification based on The Cancer Genome Atlas (TCGA) criteria, TP53, PTEN, IDH 1/2 and TERT promoter genetic analysis, EGFR amplification status, and examined their proteomic profiles against those of their parent tumors. The 20 PDGXs belonged to three of four TCGA subtypes: 8 classical, 8 mesenchymal, and 4 proneural; none neural. Amplification of EGFR gene was observed in 9 out of 20 xenografts, and of these, 3 harbored the EGFRvIII mutation. We then performed proteomic profiling of PDGX, analyzing expression/activity of several proteins including EGFR. Levels of EGFR phosphorylated at Y1068 vary considerably between PDGX samples, and this pattern was also seen in primary GBM. Partitioning of 20 PDGX into high (n=5) and low (n=15) groups identified a panel of proteins associated with high EGFR activity. Thus, PDGX with high EGFR activity represent an excellent preclinical model to develop therapies for a subset of GBM patients whose tumors are characterized by high EGFR activity. Further, the proteins found to be associated with high EGFR activity can be monitored to assess the effectiveness of targeting EGFR

Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses.

Background: Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide. Methods: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels. Results: The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%-19%), with regional variation (11%-35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%-15%]) and Eastern Asia (11% [95% CI, 10%-12%]). Bacterial serotypes I-V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%-28%), but is less frequent in some South American and Asian countries. Serotypes VI-IX are more common in Asia. Conclusions: GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts

A spindle cell carcinoma presenting with osseous metaplasia in the gingiva: a case report with immunohistochemical analysis

<p>Abstract</p> <p>Background</p> <p>Spindle cell carcinoma (SpCC) is a rare, high malignant variant of squamous cell carcinoma (SCC), which shows biphasic proliferation of conventional SCC component and malignant spindle shape cells with sarcomatous appearance.</p> <p>Methods</p> <p>A case of Spindle cell carcinoma with bone-like calcified materials, occurring at the mandibular molar region of 71-years-old Japanese male patient was presented with gross finding, histological findings and MRI image. To identify the characteristics of the bone-like materials, immunohistochemistry were performed.</p> <p>Results</p> <p>Histologically, the cancer cells were composed of spindle cells and epithelial cells which form nests with prominent keratinization. Histological findings showed typical histology of the SpCC, however, as an uncommon finding, spatters of calcified, bone-like materials were observed in between the cancer cells. Immunohistochemistry revealed that cancer cells were positive for cytokeratins and vimentin to a varying degree and negative for Desmin, S-100, Osteopontin, BMP-2 or BMP-4. These findings implied that the calcified materials were formed by metaplasia of the stromal cells.</p> <p>Discussion</p> <p>Bone-like materials formation by osseous and/or cartilaginous metaplasia of the stroma in the carcinoma has been reported. However, the detailed mechanism of these metaplasia and affection on the clinical feature, prognosis and therapies are not well established. In summary, we presented an unique case of SpCC, which has not been described in the literature.</p