Saliva Viral Load Better Correlates with Clinical and Immunological Profiles in Children with Coronavirus Disease 2019

BACKGROUND: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking. METHODS: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19. FINDINGS: 91 patients were included between March and August 2020. NPS and saliva viral loads were correlated (r=0.315, p=0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r=-0.532, p<0.001) and saliva (r=-0.417, p<0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p<0.05), and were inversely correlated with total lymphocyte (r=-0.43), CD3 (r=-0.55), CD4 (r=-0.60), CD8 (r=-0.41), B (r=-0.482), and NK (r=-0.416) lymphocyte counts (all p<0.05). Interpretation: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS

Whether to report diabetes as the underlying cause-of-death? a survey of internists of different sub-specialties

<p>Abstract</p> <p>Background</p> <p>Cause-specific mortality is a commonly used endpoint of clinical trials or prospective studies. However, it is sometimes difficult for physician to determine the underlying-cause-of-death (UCD), especially for diabetic patients coexisted with cardiovascular diseases (CVD). The aim of this survey was to examine whether internists with different specialties have different opinions on the reporting of diabetes as the UCD.</p> <p>Methods</p> <p>A total of 549 physicians completed the questionnaire in Taiwan, which comprised seven hypothetical case scenarios, each indicating a different level of contribution of diabetes in initiating the chain of events leading to death.</p> <p>Results</p> <p>As a whole, endocrinologists were more likely than cardiologists and nephrologists to report diabetes as the UCD. The differences were more prominent when the diabetic patient had a coexisting CVD. In scenario 3 (a diabetic patient with hypertension who died from acute myocardial infarction), the percentage was 56% in endocrinologists, which was significantly higher than in cardiologists (42%) and nephrologists (41%). In scenario 4 (a diabetic patient with hypertension who died from cerebrovascular infarction), the percentage was 45% in endocrinologists, and only 31% in cardiologists and 36% in nephrologists.</p> <p>Conclusions</p> <p>Internists of different sub-specialties do have different opinions on the reporting of diabetes as the UCD, especially when the diabetic patient has a coexisting CVD.</p

Luminescent Organic–Inorganic Hybrids of Functionalized Mesoporous Silica SBA-15 by Thio-Salicylidene Schiff Base

Novel organic–inorganic mesoporous luminescent hybrid material N, N′-bis(salicylidene)-thiocarbohydrazide (BSTC-SBA-15) has been obtained by co-condensation of tetraethyl orthosilicate and the organosilane in the presence of Pluronic P123 surfactant as a template. N,N′-bis(salicylidene)-thiocarbohydrazide (BSTC) grafted to the coupling agent 3-(triethoxysilyl)-propyl isocyanate (TESPIC) was used as the precursor for the preparation of mesoporous materials. In addition, for comparison, SBA-15 doped with organic ligand BSTC was also synthesized, denoted as BSTC/SBA-15. This organic–inorganic hybrid material was well-characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy (HRTEM), and photoluminescence spectra, which reveals that they all have high surface area, uniformity in the mesostructure. The resulting materials (BSTC-SBA-15 and BSTC/SBA-15) exhibit regular uniform microstructures, and no phase separation happened for the organic and the inorganic compounds was covalently linked through Si–O bonds via a self-assemble process. Furthermore, the two materials have different luminescence range: BSTC/SBA-15 presents the strong dominant green luminescence, while BSTC-functionalized material BSTC-SBA-15 shows the dominant blue emission

Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis to nitric oxide correlates with disease severity in Tegumentary Leishmaniasis

BACKGROUND: Nitric oxide (NO(•)) plays a pivotal role as a leishmanicidal agent in mouse macrophages. NO(• )resistant Escherichia coli and Mycobacterium tuberculosis have been associated with a severe outcome of these diseases. METHODS: In this study we evaluated the in vitro toxicity of nitric oxide for the promastigote stages of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis parasites, and the infectivity of the amastigote stage for human macrophages. Parasites were isolated from patients with cutaneous, mucosal or disseminated leishmaniasis, and NO(• )resistance was correlated with clinical presentation. RESULTS: Seventeen isolates of L. (L.) amazonensis or L. (V.) braziliensis promastigotes were killed by up to 8 mM of more of NaNO(2 )(pH 5.0) and therefore were defined as nitric oxide-susceptible. In contrast, eleven isolates that survived exposure to 16 mM NaNO(2 )were defined as nitric oxide-resistant. Patients infected with nitric oxide-resistant Leishmania had significantly larger lesions than patients infected with nitric oxide-susceptible isolates. Furthermore, nitric oxide-resistant L. (L.) amazonensis and L. (V.) braziliensis multiplied significantly better in human macrophages than nitric oxide-susceptible isolates. CONCLUSION: These data suggest that nitric oxide-resistance of Leishmania isolates confers a survival benefit for the parasites inside the macrophage, and possibly exacerbates the clinical course of human leishmaniasis

Epidemiology of and prenatal molecular distinction between invasive and colonizing group B streptococci in The Netherlands and Taiwan

The identification of markers for virulent group B streptococci (GBS) could guide prenatal prevention and intervention strategies. We compared the distribution of serotypes and potential pathogenicity islands (PPIs) between invasive and colonizing GBS. Colonizing and invasive strains from The Netherlands and Taiwan were serotyped. We used polymerase chain reaction (PCR) for the amplification of several new PPI markers. Several combinations of PPI-specific markers and serotypes were associated with invasiveness. For Dutch neonatal strains, a receiver operating characteristic (ROC) curve with serotype and five PPI markers showed an area under the curve (AUC) of 0.963 (95% confidence interval [CI] 0.935–0.99). For Taiwanese neonatal strains, serotype and four different PPI markers resulted in an ROC curve with an AUC of 0.894 (95% CI 0.826–0.963). PPI-specific and serological markers can distinguish local neonatal invasive GBS strains from colonizing ones. Apparently, there are clear regional differences in the GBS epidemiology and infection potential of clones

Dynamics of Envelope Evolution in Clade C SHIV-Infected Pig-Tailed Macaques during Disease Progression Analyzed by Ultra-Deep Pyrosequencing

Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of non-human primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a non-progressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep pyrosequencing. Our results showed substantial envelope variations emerging in the progressor animal after the onset of AIDS. These envelope variations impacted the length of the variable loops and charges of different envelope regions. Additionally, multiple mutations were located at the CD4 and CCR5 binding sites, potentially affecting receptor binding affinity, viral fitness and they might be selected at late stages of disease. More importantly, these envelope mutations are not random since they had repeatedly been observed in a rhesus macaque and a human infant infected by either SHIV or HIV-1, respectively, carrying the parental envelope of the infectious molecular clone SHIV-1157ipd3N4. Moreover, similar mutations were also observed from other studies on different clades of envelopes regardless of the host species. These recurring mutations in different envelopes suggest that there may be a common evolutionary pattern and selection pathway for the HIV-1 envelope during disease progression

Ionic immune suppression within the tumour microenvironment limits T cell effector function.

Tumours progress despite being infiltrated by tumour-specific effector T cells. Tumours contain areas of cellular necrosis, which are associated with poor survival in a variety of cancers. Here, we show that necrosis releases intracellular potassium ions into the extracellular fluid of mouse and human tumours, causing profound suppression of T cell effector function. Elevation of the extracellular potassium concentration ([K+]e) impairs T cell receptor (TCR)-driven Akt-mTOR phosphorylation and effector programmes. Potassium-mediated suppression of Akt-mTOR signalling and T cell function is dependent upon the activity of the serine/threonine phosphatase PP2A. Although the suppressive effect mediated by elevated [K+]e is independent of changes in plasma membrane potential (Vm), it requires an increase in intracellular potassium ([K+]i). Accordingly, augmenting potassium efflux in tumour-specific T cells by overexpressing the potassium channel Kv1.3 lowers [K+]i and improves effector functions in vitro and in vivo and enhances tumour clearance and survival in melanoma-bearing mice. These results uncover an ionic checkpoint that blocks T cell function in tumours and identify potential new strategies for cancer immunotherapy