Swab pooling enables rapid expansion of high-throughput capacity for SARS-CoV-2 community testing

Background: The challenges of rapid upscaling of testing capacity were a major lesson from the COVID-19 pandemic response. The need for process adjustments in high-throughput testing laboratories made sample pooling a challenging option to implement. / Objective: This study aimed to evaluate whether pooling samples at source (swab pooling) was as effective as qRT-PCR testing of individuals in identifying cases of SARS-CoV-2 in real-world community testing conditions using the same high-throughput pipeline. / Methods: Two cohorts of 10 (Pool10: 1,030 participants and 103 pools) and 6 (Pool6: 1,284 participants and 214 pools) samples per pool were tested for concordance, sensitivity, specificity, and Ct value differences with individual testing as reference. Results: Swab pooling allowed unmodified application of an existing high-throughput SARS-Cov-2 testing pipeline with only marginal loss of accuracy. For Pool10, concordance was 98.1% (95% Confidence interval: 93.3–99.8%), sensitivity was 95.7% (85.5–99.5%), and specificity was 100.0% (93.6–100.0%). For Pool6, concordance was 97.2% (94.0–99.0%), sensitivity was 97.5% (93.7–99.3%), and specificity was 96.4% (87.7–99.6%). Differences of outcomes measure between pool size were not significant. Most positive individual samples, which were not detected in pools, had very low viral concentration. If only individual samples with a viral concentration > 400 copies/ml (i.e. Ct value < 30) were considered positive, the overall sensitivity of pooling increased to 99.5%. / Conclusion: The study demonstrated high sensitivity and specificity by swab pooling and the immediate capability of high-throughput laboratories to implement this method making it an option in planning of rapid upscaling of laboratory capacity for future pandemics

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Prediction of Dengue Disease Severity among Pediatric Thai Patients Using Early Clinical Laboratory Indicators

Patients with severe dengue illness typically develop complications in the later stages of illness, making early clinical management of all patients with suspected dengue infection difficult. An early prediction tool to identify which patients will have a severe dengue illness will improve the utilization of limited hospital resources in dengue endemic regions. We performed classification and regression tree (CART) analysis to establish predictive algorithms of severe dengue illness. Using a Thai hospital pediatric cohort of patients presenting within the first 72 hours of a suspected dengue illness, we developed diagnostic decision algorithms using simple clinical laboratory data obtained on the day of presentation. These algorithms correctly classified near 100% of patients who developed a severe dengue illness while excluding upwards of 50% of patients with mild dengue or other febrile illnesses. Our algorithms utilized white blood cell counts, percent white blood cell differentials, platelet counts, elevated aspartate aminotransferase, hematocrit, and age. If these algorithms can be validated in other regions and age groups, they will help in the clinical management of patients with suspected dengue illness who present within the first three days of fever onset

Differential Gene Expression Changes in Children with Severe Dengue Virus Infections

Dengue virus infection is an impressively emerging disease that can be fatal in severe cases. It is not precisely clear why some patients progress to severe disease whereas most patients only suffer from a mild infection. In severe disease, a “cytokine storm” is induced, which indicates the release of a great number of inflammatory mediators (“cytokines”). Evidence suggested that a balance could be involved between protective and pathologic cytokine release patterns. We studied this concept in a cohort of Indonesian children with severe dengue disease using a gene expression profiling method

Currents issues in cardiorespiratory care of patients with post-polio syndrome

ABSTRACT Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute attack of the poliomyelitis virus. Most often, polio survivors experience a gradual new weakening in muscles that were previously affected by the polio infection. The actual incidence of cardiovascular diseases (CVDs) in individuals suffering from PPS is not known. However, there is a reason to suspect that individuals with PPS might be at increased risk. Method A search for papers was made in the databases Bireme, Scielo and Pubmed with the following keywords: post polio syndrome, cardiorespiratory and rehabilitation in English, French and Spanish languages. Although we targeted only seek current studies on the topic in question, only the relevant (double-blind, randomized-controlled and consensus articles) were considered. Results and Discussion Certain features of PPS such as generalized fatigue, generalized and specific muscle weakness, joint and/or muscle pain may result in physical inactivity deconditioning obesity and dyslipidemia. Respiratory difficulties are common and may result in hypoxemia. Conclusion Only when evaluated and treated promptly, somE patients can obtain the full benefits of the use of respiratory muscles aids as far as quality of life is concerned

Interleukin-4 Alters Early Phagosome Phenotype by Modulating Class I PI3K Dependent Lipid Remodeling and Protein Recruitment

Phagocytosis is a complex process that involves membranelipid remodeling and the attraction and retention of key effector proteins. Phagosome phenotype depends on the type of receptor engaged and can be influenced by extracellular signals. Interleukin 4 (IL-4) is a cytokine that induces the alternative activation of macrophages (MΦs) upon prolonged exposure, triggering a different cell phenotype that has an altered phagocytic capacity. In contrast, the direct effects of IL-4 during phagocytosis remain unknown. Here, we investigate the impact of short-term IL-4 exposure (1 hour) during phagocytosis of IgG-opsonized yeast particles by MΦs. By time-lapse confocal microscopy of GFP-tagged lipid-sensing probes, we show that IL-4 increases the negative charge of the phagosomal membrane by prolonging the presence of the negatively charged second messenger PI(3,4,5)P3. Biochemical assays reveal an enhanced PI3K/Akt activity upon phagocytosis in the presence of IL-4. Blocking the specific class I PI3K after the onset of phagocytosis completely abrogates the IL-4-induced changes in lipid remodeling and concomitant membrane charge. Finally, we show that IL-4 direct signaling leads to a significantly prolonged retention profile of the signaling molecules Rac1 and Rab5 to the phagosomal membrane in a PI3K-dependent manner. This protracted early phagosome phenotype suggests an altered maturation, which is supported by the delayed phagosome acidification measured in the presence of IL-4. Our findings reveal that molecular differences in IL-4 levels, in the extracellular microenvironment, influence the coordination of lipid remodeling and protein recruitment, which determine phagosome phenotype and, eventually, fate. Endosomal and phagosomal membranes provide topological constraints to signaling molecules. Therefore, changes in the phagosome phenotype modulated by extracellular factors may represent an additional mechanism that regulates the outcome of phagocytosis and could have significant impact on the net biochemical output of a cell